ABCC7 p.Asn1303Lys

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PMID: 16006996 [PubMed] Conseil G et al: "Polymorphisms of MRP1 (ABCC1) and related ATP-dependent drug transporters."
No. Sentence Comment
56 In the kidney, glomeruli and distal collecting tubules express MRP1, and, in the brain, MRP1 appears to form part of the drug permeability barrier Fig. 1 CF (CFTR/ABCC7) Q1291R E1228G Q1238R G1244E/V G1247R G1249R S1251N S1255P/L W1282G/R/C R1283K/M N1303K Y1307C E1321Q K1351E Q1352H R1268Q V1298F T1301I G1302R A1303P R1314W/Q G1321S R1339C Q1347H I1350L G1354R D1361N Q1382R A1450T R1347E R1351P V1359G/M S1368A G1377R G1382S R1392H R1419C R1435Q G1477R G1479R R1492W E1505K DJS (MRP2/ABCC2) NBD1 NBD2 COOH MEMBRANE MSD MSD MSD 12131415161710116 7 8 91 23 4 5TM H2 N Extracellular Intracellular PXE (ABCC6) PHHI (SUR1/ABCC8) Two-dimensional structure of MRP-related proteins.
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ABCC7 p.Asn1303Lys 16006996:56:250
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PMID: 16442101 [PubMed] Frelet A et al: "Insight in eukaryotic ABC transporter function by mutation analysis."
No. Sentence Comment
299 [137] Q493A, Q1291A, N505C, N1303K Q493A and N505C reduced and increased the frequency of CO, respectively.
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ABCC7 p.Asn1303Lys 16442101:299:28
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PMID: 10050655 [PubMed] Lissens W et al: "Molecular analysis of the cystic fibrosis gene reveals a high frequency of the intron 8 splice variant 5T in Egyptian males with congenital bilateral absence of the vas deferens."
No. Sentence Comment
32 Initially, eight of the males` samples were analysed by a commercial kit allowing the detection of eight mutations in the CFTR gene: ∆F508, ∆I507, G542X, G551D, R553X, 1717-1G→A, W1282X and N1303K (INNO-LiPA CF, Innogenetics, Zwijnaarde, Belgium).
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ABCC7 p.Asn1303Lys 10050655:32:211
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PMID: 10077727 [PubMed] Loumi O et al: "Analysis of the complete coding region of the CFTR gene in ten Algerian cystic fibrosis families."
No. Sentence Comment
17 CF mutations and variants detected in Algerian patients (n = 20 CF chromosomes) Mutations Localization n % Cum fr. del CTT exon 10 4 20 20 N1303K C→G 4041 exon 21 4 20 40 711+1G→T G→T711+1 intron 5 2 10 50 1812-1G→A G→A 1812-1 intron 11 1 5 55 V754M G→A 2392 exon 13 1 5 60 Total 12 60 Table 1b. Variants detected in Algerian subjects (n = 40 chromosomes) Variants Localization n % A→G 1540 exon 10 8 20 P1290P A→G 4002 exon 20 1 2.5 T854T T→G 2694 exon 14a 11 27.5 Q1463Q G→A 4521 exon 24 7 17.5 875+40A→G intron 6a 2 5 5T intron 8 1 2.5 n = number of chromosomes; cum.
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ABCC7 p.Asn1303Lys 10077727:17:139
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27 Among the 16 CF chromosomes carrying an unidentified mutated allele, 4 different mutations were identified, as reported in table 1a: N1303K (20%), 711 + 1G→T (10%), V754M (5%), 1812 - 1G→A (5%).
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ABCC7 p.Asn1303Lys 10077727:27:133
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31 The N1303K mutation has already been reported to be significantly more common in Southern European populations than in Northern European populations (Cystic Fibrosis Consortium).
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ABCC7 p.Asn1303Lys 10077727:31:4
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55 In our study, we identified 3 homozygous CF patients: 'F508/'F508, N1303K/N1303K, 711 + 1G→T/711 + 1G→T.
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ABCC7 p.Asn1303Lys 10077727:55:67
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ABCC7 p.Asn1303Lys 10077727:55:74
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57 The N1303K/N1303K homozygous patient from related parents was a 4-year-old girl with pancreatic insufficiency and serious pulmonary disease with P. aeruginosa colonization, and 3 positive sweat chloride tests confirmed the CF diagnosis.
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ABCC7 p.Asn1303Lys 10077727:57:4
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ABCC7 p.Asn1303Lys 10077727:57:11
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74 Four other mutations have been identified: Hum Hered 1999;49:81-84 Loumi/Baghriche/Delpech/Kaplan/ Bienvenu N1303K (20%), 711 + 1G→T (10%), 1812 - 1G→A (5%) and V754M (5%).
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ABCC7 p.Asn1303Lys 10077727:74:110
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PMID: 10099982 [PubMed] Dohle GR et al: "The complex relationships between cystic fibrosis and congenital bilateral absence of the vas deferens: clinical, electrophysiological and genetic data."
No. Sentence Comment
58 CFTR mutation analysis was performed for 10 mutations: we analysed for the mutations R117H, A455E, ∆F508, 1717-1G→A, G542X, R553X, R1162X, S1251N, W1282X, and N1303K.
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ABCC7 p.Asn1303Lys 10099982:58:173
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PMID: 10229049 [PubMed] Lecoq I et al: "Blood immunoreactive trypsinogen concentrations are genetically determined in healthy and cystic fibrosis newborns."
No. Sentence Comment
61 Twins or unrelated patients with identical genotype had very similar neonatal IRT concentrations: DF508/I148T (twins), 1040 and 1055 mg LÀ1 ; N1303K/G149R (twins), 1600 and 1725 mg LÀ1 ; DF508/E585X, 900 and 945 mg LÀ1 ; DF508/ G542X, 1535 and 1660 mg LÀ1 ; DF508/L206W, 980, 1090 and 1100 mg LÀ1 .
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ABCC7 p.Asn1303Lys 10229049:61:147
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72 In this study, CF newborns with one mutation in an exon encoding for either NBD1 or NBD2 (DF508, G542X, G551D, E585X, N1303K, etc.) and the other affecting one of the MSD (R117H, 574delA, I148T, G149R, L206W, etc.) had significantly lower IRT concentrations than CF neonates with both mutations located in NBD.
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ABCC7 p.Asn1303Lys 10229049:72:118
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PMID: 10325788 [PubMed] Sarles J et al: "Blood concentrations of pancreatitis associated protein in neonates: relevance to neonatal screening for cystic fibrosis."
No. Sentence Comment
77 Other genotypes were F508/G542X (n=4), F508/N1303K (n=2), F508/I148T (n=2), F508/R117H, F508/R553X, F508/1717-1G->A, F508/ 1078delT, F508/2789+5G->A, F508/ E1308X (a novel CFTR mutation), R553X/ 394delTT, and N1303K/R553X.
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ABCC7 p.Asn1303Lys 10325788:77:44
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ABCC7 p.Asn1303Lys 10325788:77:209
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PMID: 10341008 [PubMed] Boucher D et al: "Screening for cystic fibrosis transmembrane conductance regulator gene mutations in men included in an intracytoplasmic sperm injection programme."
No. Sentence Comment
3 In 10 out of 14 patients with CAVD, CFTR mutations were found; nine patients had one ∆∆F508 mutation and one patient had two CFTR mutations (N1303K/R117H).
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ABCC7 p.Asn1303Lys 10341008:3:155
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51 Each patient was tested for the nine most frequent cystic fibrosis-causing CFTR mutations: ∆F508, ∆I507, 1717-1G→A, G542X, G551D, R553X, W1282X, N1303K, 621ϩ1G→T and the three most frequent CFTR mutations involved in CBAVD (∆F508, R117H and the IVS8 polyT).
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ABCC7 p.Asn1303Lys 10341008:51:166
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53 The other mutations were detected using either heteroduplex analysis (∆I507), allele specific oligonucleotide (ASO) hybridization (G542X, 1717-1G→A, IVS8 polyT) (Kerem et al., 1990), restriction endonuclease analysis (G551D, R553X, W1282X) (Zielenski et al., 1991) or polymerase chain reaction (PCR)-mediated site-directed mutagenesis (621ϩ1G→T, R117H, N1303K) (Friedman et al., 1991).
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ABCC7 p.Asn1303Lys 10341008:53:380
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60 Restriction digestion and electrophoresis (Figures 2 and 3) Detection of 621ϩ1G→T, R117H, G551D, R553X, W1282X and N1303K were performed using appropriate restriction enzymes (New England Biolabs, Ozyme, Saint Quentin Yvelines, France) as described in Table IV.
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ABCC7 p.Asn1303Lys 10341008:60:128
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64 Clinical status, semen characteristics and concentrations of follicle stimulating hormone (FSH) in azoospermic patients No. Plasma FSH Semen volume Semen pH Semen fructose Semen Semen carnitine CFTR genotype (mIU/ml) (ml) (µmoles) α-glucosidase (mIU) (nmoles) Patients with congenital absence of the vas deferens (CAVD) 1 4.5 0.7 6.5 0 3 20 ∆F508/N 9T/5T 2 6.9 0.5 6.8 - - - ∆F508/N 9T/7T 3 1.9 0.2 6.5 Ͻ1 - - ∆F508/N 9T/5T 4 0.7 0.5 6.8 0 3 20 ∆F508/N 9T/7T 5 6.0 0.3 6.8 - - - ∆F508/N 9T/5T 6 3.6 0.5 6.5 - 3 20 ∆F508/N 9T/5T 7 4.0 1.5 6.5 - - - ∆F508/N 9T/5T 8 5.9 1.2 6.5 0 4 20 ∆F508/N 9T/7T 9 3.8 - - - - - ∆F508/N 9T/5T 10 5.0 - - 0 - 24 N1303K/ 9T/7T R117H *11 2.0 0.8 7.1 0 2 - N/N 9T/7T 12 4.3 0.3 7.4 0 - 3.6 N/N 7T/7T 13 1.0 0.4 6.5 0 - - N/N 9T/5T 14 2.0 1.3 6.8 0 5 - N/N 9T/5T Patients without CAVD 15 7.4 1.8 8.3 29 1 126 N/N 7T/7T 16 - 2.2 8.5 33 20 154 N/N 7T/7T 17 - 4.4 8.3 35 12 352 N/N 7T/7T 18 3.6 8.5 8.1 187 82 680 N/N 7T/7T 19 3.1 2.5 8.5 25 - 100 N/N 7T/7T 20 3.4 0.4 6.5 Ͻ1 7 28 N/N 7T/5T 21 1.6 1.4 8.3 4.2 5 126 N/N 7T/9T 22 3.1 3.0 8.7 78 2 270 N/N 7T/7T 23 0.9 3.0 9.0 - - - N/N 7T/7T 24 4.4 10.0 7.9 190 - 300 N/N 7T/7T 25 1.3 2.2 8.1 40 - 44 N/N 7T/7T 26 2.9 2.6 8.3 26 8 286 N/N 7T/7T 27 1.7 2.1 8.3 44 - 84 N/N 7T/7T 28 - 9.0 8.1 180 27 540 N/N 7T/7T 29 - 1.5 8.3 23 - 120 N/N 7T/7T 30 4.1 0.3 7.1 - - - N/N 7T/7T 31 4.9 1.7 8.3 20 20 - N/N 7T/7T 32 7.2 1.0 7.9 Ͻ1 3 30 N/N 7T/7T 33 9.0 1.5 6.5 Ͻ1 2 - N/N 7T/5T 34 11.7 5.0 7.9 90 - 400 N/N 7T/7T 35 7.2 4.6 8.1 92 132 1518 N/N 7T/9T 36 4.4 2.5 8.1 30 11 1510 N/N 7T/7T 37 14 3.6 8.3 50 27 900 N/N 7T/7T 38 4.9 6.0 7.9 72 - 300 N/N 7T/7T 39 6.0 1.8 8.3 31 17 252 N/N 7T/7T 40 14.3 1.5 8.3 22 1 90 N/N 7T/9T 41 6.6 2.2 - 27 - 290 N/N 7T/7T 42 4.8 0.5 6.8 0 3 42 N/N 7T/7T 43 13.9 2.0 7.8 - - - N/N 7T/7T 44 3.9 3.9 8.3 47 11 - N/N 7T/7T 45 1.5 1.8 8.6 11 - - N/N 7T/7T 46 4.2 3.0 8.5 25 28 210 N/N 7T/7T 47 4.0 5.8 7.9 122 42 696 N/N 7T/9T 48 16.3 5.0 8.7 145 68 900 N/N 7T/7T 49 7.2 4.0 7.5 - - - N/N 7T/5T 50 8.0 4.3 8.1 34 200 1284 N/N 7T/7T 51 23.9 0.8 9.0 5.6 17 184 N/N 7T/7T 52 - 2.2 8.5 35 - 308 N/N 7T/9T 53 17.8 3.1 8.1 31 50 527 N/N 7T/7T Fructose, α glucosidase and carnitine are expressed per ejaculate.
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ABCC7 p.Asn1303Lys 10341008:64:725
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74 One patient was a compound heterozygote, R117H/N1303K.
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ABCC7 p.Asn1303Lys 10341008:74:47
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94 Methods for detecting mutations Mutation Method R117H PCR-mediated-site-directed mutagenesis, HaeII digestion N: 113 ϩ 24 bp R117H: 137 bp 621ϩ1G→T MseI digestion N: 269 ϩ 33 bp 621ϩ1G→T: 215 ϩ 54 ϩ 33 bp IVS8polyT ASO hybridization: hybridization at 50°C 5T: TGT GTG TGT TTT TAA CAG washing at 55°C 7T: TGT GTG TTT TTT TAA CAG washing at 51°C 9T: GTG TGT TTT TTT TTA ACA G washing at 55°C ∆I507 Heteroduplex DNA formation ∆F508 Heteroduplex DNA formation (see Figure 1) 17171G→A ASO hybridization, hybridization at 42°C, washing at 54°C N: TTT GGT AAT AGG ACA TCT CC 17171G→A: TTT GGT AAT AAG ACA TCT CC G542X ASO hybridization, hybridization at 42°C, washing at 49°C N: ACC TTC TCC AAG AAC T G542X: ACC TTC TCA AAG AAC T G551D DpnII digestion: N: 425 bp G551D: 243 ϩ 182 bp R553X HincII digestion N: 239 ϩ 186 bp R553X: 425 bp W1282X MnlI digestion N: 178 ϩ 172 ϩ 123 bp W1282X: 301 ϩ 172 bp N1303K PCR-mediated-site-directed mutagenesis, BstNI digestion N: 266 ϩ 23 bp N1303K: 289 bp The underlining indicates the location of nucleotide substitution in normal and mutated allele.
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ABCC7 p.Asn1303Lys 10341008:94:1042
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ABCC7 p.Asn1303Lys 10341008:94:1126
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99 Our results are in accordance with these data, since nine of the 14 patients (64.2%) with CAVD were heterozygous for one CFTR mutation (∆F508) and one patient with CBAVD (7.1%) was a compound heterozygote (R117H/N1303K) and was 7T/9T.
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ABCC7 p.Asn1303Lys 10341008:99:219
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100 N1303K is classified as a severe mutation with respect to pancreatic status in CF patients.
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ABCC7 p.Asn1303Lys 10341008:100:0
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127 Detection of the mutation N1303K by polymerase chain reaction (PCR).
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ABCC7 p.Asn1303Lys 10341008:127:26
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130 Lane 1: 1 kb DNA ladder (Life Technologies, Cergy-Pontoise, France); Lanes 2 and 6: heterozygote for the N1303K mutation; Lanes 3, 4, 5, 7: normal homozygote; Lane 8: BstNI cut control DNA; Lane 9: uncut control DNA.
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ABCC7 p.Asn1303Lys 10341008:130:105
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PMID: 10376575 [PubMed] Mak V et al: "Proportion of cystic fibrosis gene mutations not detected by routine testing in men with obstructive azoospermia."
No. Sentence Comment
28 Analysis for 31 of the most common CFTR mutations found within the white CF population,60 consisting of ⌬F508, W1282X, G542X, G551D, N1303K, R553X, G85E, R117H, S549N, V520F, R334W, A455E, R347P, R1162X, Y122X, S549R, 621+1G→T, ⌬I507, R560T, R347H, 3659delC, Q493X, 1898+1G→T, 711+1G→T, 3849+10C→T, 1717-1G→A, 3849+4A→G, 3905insT, 1078delT, 2183AA→G, and 2789+5G→A. Briefly, the technique involved amplification by polymerase chain reaction61 of the relevant exons, followed by digestion with appropriate restriction endonucleases and acrylamide gel electrophoresis with ethidium bromide staining.
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ABCC7 p.Asn1303Lys 10376575:28:140
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45 (%) Men With 2 Mutations ⌬F508/IVS8-5T 7 (11) ⌬F508/IVS8-5T 1 (10) ⌬F508/IVS8-5T 1 (1.8) ⌬F508/R117H 6 (9) W1282X/IVS8-5T 1 (1.8) ⌬F508/L206W 1 (1.6) G544S/IVS8-5T 1 (1.8) ⌬F508/M952T 1 (1.6) V754M/-741T→G 1 (1.8) ⌬F508/P67L 1 (1.6) R75Q/R258G 1 (1.8) ⌬F508/S549R 1 (1.6) R334W/R334W 1 (1.6) R117H/R117H 1 (1.6) R117H/IVS8-5T 1 (1.6) R347P/IVS8-5T 1 (1.6) N1303K/IVS8-5T 1 (1.6) 1677delTA/IVS8-5T 1 (1.6) R117L/IVS8-5T 1 (1.6) D979A/IVS8-5T 1 (1.6) IVS8-5T/IVS8-5T 1 (1.6) Men With 1 Mutation IVS8-5T/N 10 (16) ⌬F508/N 1 (10) IVS8-5T/N 9 (16) ⌬F508/N 1 (2) ⌬F508/N 6 (9) IVS8-5T/N 1 (10) ⌬F508/N 1 (1.8) G542X/N 1 (2) W1282X/N 2 (3) R75Q/N 1 (1.8) IVS8-5T/N 5 (10) L206W/N 1 (1.6) W1282X/N 1 (1.8) 4016insT/N 1 (1.6) R117H/N 1 (1.8) 2423delG/N 1 (1.8) Men With No Mutations 18 (28) 7 (70) 37 (66) 42 (86) *N indicates that no CFTR mutations or variants were detected.
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ABCC7 p.Asn1303Lys 10376575:45:419
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47 tion panel included W1282X (2 alleles), R334W (2 alleles), S549R (1 allele), R347P (1 allele), and N1303K (1 allele).
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ABCC7 p.Asn1303Lys 10376575:47:99
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58 (%) 31 Mutation panel† ⌬F508 23 (18) ⌬F508 2 (10) ⌬F508 2 (1.8) ⌬F508 1 (1) R117H 9 (7) W1282X 2 (1.8) G542X 1 (1) W1282X 2 (1.6) R117H 1 (0.9) R334W 2 (1.6) S549R 1 (0.8) R347P 1 (0.8) N1303K 1 (0.8) Extensive screen† ⌬F508 23 (18) ⌬F508 2 (10) ⌬F508 2 (1.8) ⌬F508 1Mutations included in R117H 9 (7) W1282X 2 (1.8) G542X 131 mutation panel W1282X 2 (1.6) R117H 1 (0.9) R334W 2 (1.6) S549R 1 (0.8) R347P 1 (0.8) N1303K 1 (0.8) L206W 2 (1.6)‡ R75Q 2 (1.8)‡Mutations not included in P67L 1 (0.8)‡ G544S 1 (0.9)‡31 mutation panel 1677delTA 1 (0.8)‡ 2423delG 1 (0.9)‡ R117L 1 (0.8)‡ V754M 1 (0.9)‡ 4016insT 1 (0.8)‡ -741T→G 1 (0.9)‡ D979A 1 (0.8)§ R258G 1 (0.9)§ M952T 1 (0.8)¶ IVS8-5T 25 (20)# 2 (10) 12 (11) 5 (5) Detectable mutations 72 (56)# 4 (20) 24 (21)# 7 (7) Detectable mutations missed by 31 mutation panel 33 (46) 2 (50) 19 (79) Detectable non-IVS8-5T mutations missed by 31 mutation panel 8 (17) 0 (0) 7 (58) *Percentages indicate allele frequency.
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ABCC7 p.Asn1303Lys 10376575:58:221
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ABCC7 p.Asn1303Lys 10376575:58:482
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83 These severe CFTR gene mutations are associated with pancreatic insufficiency and are generally class 1 through 3 mutations: ⌬F508, W1282X, N1303K, S549R, 1677delTA, R117L, 4016insT, G544S, 2423delG, V754M, and 741T→G.
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ABCC7 p.Asn1303Lys 10376575:83:147
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PMID: 10388469 [PubMed] Castaldo G et al: "Detection of five rare cystic fibrosis mutations peculiar to Southern Italy: implications in screening for the disease and phenotype characterization for patients with homozygote mutations."
No. Sentence Comment
13 A few mutations (i.e., ⌬F508, N1303K, G542X, and R553X) are frequent worldwide; the other mutations are regional or "private" mutations.
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ABCC7 p.Asn1303Lys 10388469:13:37
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36 All patients were first analyzed for eight CF mutations, i.e., ⌬F508, N1303K, G542X, W1282X, 1717-1G3A, R553X, 2183AA3G, and I148T (9).
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ABCC7 p.Asn1303Lys 10388469:36:77
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39 methods The eight CF mutations (i.e., ⌬F508, N1303K, G542X, W1282X, 1717-1G3A, R553X, 2183AA3G, and I148T) were identified with a semi-automated procedure based on a single multiplex PCR amplification followed by the allele-specific oligonucleotide (ASO) identification we described previously (9).
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ABCC7 p.Asn1303Lys 10388469:39:52
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PMID: 10392242 [PubMed] Bucholtz GA et al: "The cystic fibrosis conductance regulator gene exon sequence is normal in a patient with edematous eosinophilic nasal polyps."
No. Sentence Comment
11 12,13 Burger et al. analyzed 112 nasal polyp specimens from non-CF patients for 8 cystic fibrosis conductance regulator (CFTR) gene mutations (Ll508, Ll] 507, D 11OH, TI17H, 621+ IG---7T, N1303K, G551D, R553X).14 Ho- Delivered by Publishing Technology to: University of North Carolina IP: 152.19.83.63 On: Mon, 08 Aug 2011 14:07:01 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to www.copyright.com mozygous or compound heterozygous individuals were not found.
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ABCC7 p.Asn1303Lys 10392242:11:188
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PMID: 10402399 [PubMed] Jakubiczka S et al: "Frequency of CFTR gene mutations in males participating in an ICSI programme."
No. Sentence Comment
13 Materials and methods CFTR screening included the most frequent CFTR mutations in the German population (R347P, ∆F508, G542X, S549I,N,R(A→C), G551D, R553X, N1303K, and 3849ϩ10kbC→T) (Do¨rk et al., 1994) as well as the mutation R117H and the analysis of the IVS8-T haplotype.
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ABCC7 p.Asn1303Lys 10402399:13:170
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PMID: 10439967 [PubMed] Liechti-Gallati S et al: "Two buffer PAGE system-based SSCP/HD analysis: a general protocol for rapid and sensitive mutation screening in cystic fibrosis and any other human genetic disease."
No. Sentence Comment
20 The distribution of analysed known mutations is similar to that of the total number of mutations in the entire CFTR gene: missense mutations account for 35% (G27E, G85E, R117H, A120T, I148T, H199Y, R334W, T338I, R347P, R347H, A455E, M718K, S5449N, S5449I, G551D, R560T, R560S, S945L, S977P, I1005R, R1066C, R1070Q, M1101K, D1152H, S1235R, R1283M, N1303K, N1303H), followed by 28% of frameshift mutations (175delC, 394delTT, 457TAT- > G, 905delG, 1078delT, I507, F508, 1609delCA, 1677delTA, 2143delT, 2176insC, 218delA, 2184insA, 2869insG, 3659delC, 3732delA, 3821delT, 3905insT, 4016insT, 4172delGC, 4382delA), 21% of nonsense mutations (Q30X, Q39X, Q220X, W401X, Q525X, G542X, Q552X, R553X, V569X, E585X, K710X, R792X, Y1092X, R1162X, S1255X, W1282X, E1371X), and 16% of splice site mutations (621 + 1G- > T, 711 + 1G- > T, 711 + 5G- > A, 1717-1G- > A, 1898 + 1G- > A, 1898 + 5G- > T, 2789 + 5G- > A, 3271 + 1G- > A, 3272-26A- > G, 3601-17T- > C, 3849 + 4A- > G, 3849 + 10kbC- > T, 4374 + 1G- > T).
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ABCC7 p.Asn1303Lys 10439967:20:347
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22 Polymerase Chain Reaction Amplification The 27 exons (including exon/intron boundaries) as well as intron 19 of the CFTR gene were amplified by the polymerase chain reaction (PCR)13 using approximately 200 ng of genomic DNA, 10 mM dNTPs (PCR Nucleotide Mix, Boehringer/ Roche Diagnostics Rotkreuz, ZG, Switzerland), 10 mM Tris (pH 8.3), 50 mM KCl, 1.5 mM MgCl2, 2.5 unit Taq polymerase (Boehringer/Roche Diagnostics Rotkreuz, ZG, Switzerland) and 20 pmol of each primer in a total volume of 50 µl. Twenty-eight cycles of PCR with denaturation at 94°C for 15 s, annealing at either 61°C (exons 1, 2, 5-12, 13CD, 15, 16, 18-22, 24) or 53°C (exons 3, 4, 13AB, 14a, 14b, 17a, 17b, 21/N1303K, 23) for 15 s and extension at 72°C for 45 s were carried out in PE 9600 and PE 2400 thermocyclers.
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ABCC7 p.Asn1303Lys 10439967:22:700
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24 Sequences for the primers 1-10, 11 (forward), 12-16, 17b, 18-20, 21 (forward), 22, 23, 24 (forward) have been reported by Zielenski et al;14 exon 17a was amplified using the primer sequences described by Cheadle et al;15 the primers for the amplification of intron 19 were designed by Highsmith et al;16 and the primer sequence for the detection of N1303K was reported by Friedman et al.17 The following primer sequences were derived from the present study: Exon 11 (reverse): 5' - GTGATTCTTAACCCAC- TAGCC - 3' Exon 21 (reverse): 5' - AAGTGTGTAGAATGATGT- CAGC - 3' Exon 24 (reverse): 5' - CGAGCTCCAATTCCAT- GAGG - 3' SSCP Analysis Three microliters of the amplification product were added to 2-3 µl of SSCP buffer (95% formamide, 100 mM NaOH, 0.25% bromphenol blue, 0.25% xylencyanol) and denatured at 95°C for 2 min followed by rapid cooling on ice. Three microliters of the mixture were loaded on to a 12% nondenaturing polyacrylamide gel (99% acrylamide, 1% piperazine diacrylamide (PDA)) cast on to GelBond (Bioconcept, Allschwil, BL, Switzerland).
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ABCC7 p.Asn1303Lys 10439967:24:350
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34 Intron 19, all 27 exons and their exon-intron boundaries, including the 24 most common mutations worldwide (G85E, R117H, 621 + 1G- > T, 711 + 1G- > T, 1078delT, R334W, R347P, A455E, I507, F508, 1717-1G- > A, G542X, S549N, G551D, R553X, R560T, 1898 + 1G- > A, 2184delA, 2789 + 5G- > A, R1162X, 3659delC, 3849 + 10kbC- > T, W1282X, N1303K) (Cystic Fibrosis Genetic Analysis Consortium 1994), and the 15 most common mutations in our population (I148T, 1078delT, R334W, R347P, F508, 1717-1G- > A, G542X, R553X, 2347delG, D1152H, R1162X, 3849 + 10kbC- > T, 3905insT, W1282X, N1303K), were considered in this study.
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ABCC7 p.Asn1303Lys 10439967:34:330
status: NEW
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ABCC7 p.Asn1303Lys 10439967:34:570
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92 The technique developed demonstrates excellent single-strand separation and non-radioactive visualisation on polyacrylamide gels, and is time-saving and directly Table 2 Known mutations identified in 198 CF patients analysed investigatively Exon (E) Number of CFTR mutations intron (I) chromosomes Patient`s nationality Highest prevalence ∆F508 E10 212 miscellaneous 3905insT E20 025 Swiss Swiss, Amish, Arcadian R553X E11 020 Swiss, German German 1717-1G->A I10 017 Swiss, Italian Italian N1303K E21 011 Swiss, French, Italian Italian W1282X E20 014 Swiss, Italian, Israelit Jewish-Askhenazi G542X E11 009 Swiss, Spanish, Italian Spanish 2347delG E13 008 Swiss R1162X E19 006 Swiss, Italian, Russian Italian 3849+10kbC->T I19 005 German, French R347P E07 004 Swiss T5 I08 004 Swiss R334W E07 003 Swiss Q525X E10 003 Swiss 3732delA E19 003 Swiss S1235R E19 003 Italian, Turkish G85E E03 002 Italian, Greek I148T E04 002 Austrian, Turkish French-Canadian 621+1G->T I04 002 French French-Canadian 1078delT E07 002 Swiss E585X E12 002 Italian 2176insC E13 002 Swiss, Italian 2789+5G->A I14b 002 Italian Spanish D1152H E18 002 Swiss, French 4016insT E21 002 Turkish Q39X E02 001 Swiss 394delTT E03 001 Swiss Nordic, Finnish R117H E04 001 Swiss A120T E04 001 Swiss G126D E04 001 Swiss 711+5G->A I05 001 Russian M348K E07 001 Italian L568F E12 001 Italian 2183AA->G E13 001 Italian Italian K710X E13 001 Swiss S945L E15 001 French 3272-26A.->G I17a 001 Swiss M1101K E17b 001 Swiss Huttite 3601-17C->T I18 001 Swiss R1158X E19 001 Swiss 4005+1G-A I20 001 Italian applicable to early diagnostic testing, carrier detection and prenatal diagnosis.
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ABCC7 p.Asn1303Lys 10439967:92:497
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PMID: 10444722 [PubMed] Gasparini P et al: "Analysis of 31 CFTR mutations by polymerase chain reaction/oligonucleotide ligation assay in a pilot screening of 4476 newborns for cystic fibrosis."
No. Sentence Comment
8 Other common mutations included G542X (16 of 144), which was particularly common in southern Italy (14 of 49), N1303K (8 of 144), and R117H (8 of 144), detected only in the northern centres.
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ABCC7 p.Asn1303Lys 10444722:8:111
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45 Other mutations found with greater than normal frequency were G542X, which is particularly common in southern Italy (14 of 49 individuals from San Giovanni Rotondo), N1303K (8 of 144), and R117H (8 of 144), which was detected only in the northern centres.
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ABCC7 p.Asn1303Lys 10444722:45:166
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46 Table 1 Mutations analysed in the CFTR gene using polymerase chain reaction/oligonucleotide litigation assay/sequence coded separation Mutation Location Nucleotide Result F508 Exon 10 3 bp deletion Deletion of Phe-508 I507 Exon 10 3 bp deletion Deletion of Ile-507 (or -506) Q493X Exon 10 C-1609 →→ T Gln-493 → Stop V520F Exon 10 G-1690 → T Val-520 → Phe 1717-1G → A Intron 10 G-1717-1 → A 3`-splice site mutation G542X Exon 11 G-1756 → T Gly-542 → Stop G551D Exon 11 G-1784 → A Gly-551 → Asp R553X Exon 11 C-1789 → T Arg-553 → Stop R560T Exon 11 G-1811 → C Arg-560 → Thr S549R Exon 11 T-1779 → G Ser-549 → Arg S549N Exon 11 G-1778 → A Ser-549 → Asn 3849+10 kb C → T Intron 19 C-3849+10 kb → T Splice mutation 3849+4A → G Intron 19 A-3849+4 → G Splice mutation R1162X Exon 19 C-3616 → T Arg-1162 → Stop 3659delC Exon 19 1 bp deletion Frameshift W1282X Exon 20 G-3978 → A Trp-1282 → Stop 3905insT Exon 20 1 bp insertion Frameshift N1303K Exon 21 C-4041 → G Asn-1303 → Lys G85E Exon 3 G-386 → A Gly-85 → Glu 621+1G → T Intron 4 G-621+1 → T 5`-splice site mutation R117H Exon 4 G-482 → A Arg-117 → His Y122X Exon 4 T-498 → A Tyr-122 → Stop 711+1G → T Intron 5 G-711+1 → T 5`-splice site mutation 1078delT Exon 7 1 bp deletion Frameshift R347P Exon 7 G-1172 → C Arg-347 → Pro R347H Exon 7 G-1172 → A Arg-347 → His R334W Exon 7 C-1132 → T Arg-334 → Trp A455E Exon 9 C-1496 → A Ala-455 → Glu 1898+1G → A Intron 12 G-1898+1 → A 5`-splice site mutation 2184delA Exon 13 Deletion A-2184; A-2183 → G Frameshift 2789+5G → A Intron 14B G-2789+5 → A Splice mutation Table 2 Summary of cystic fibrosis screening results No of samples analysed Normal subjects Carriers Carrier frequency Turin 1574 1521 53 1/29.7 Pavia 1341 1299 42 1/31.9 San Giovanni Rotondo 1561 1512 49 1/31.8 Total 4476 4332 144 1/31.1 Table 3 Detailed list of mutations detected in the Italian population Centre F508 G542X R347P 2183-AG N1303K 711+1GT 1717-1A R347H R117H 1898+1G 2789+5G W1282X R1162X I507 Other TO 33 2 1 1 5 1 1 2 3 2 2 - - - PV 27 - - 1 2 - 1 - 5 - 1 2 1 1 SGR 30 14 2 1 1 1 - - - - - - - - TO, Dipartimento di Patologia Clinica, Ospedale Infantile "Regina Margherita, Torino; PV, Istituto di Anatomia Patologica, Sezione di Anatomia Patologica, Università di Pavia, Pavia; SGR, Servizio di Genetica Medica and Divisione di Neonatologia, IRCCS Casa Sollievo della SoVerenza, San Giovanni Rotondo, Foggia.
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ABCC7 p.Asn1303Lys 10444722:46:1119
status: NEW
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ABCC7 p.Asn1303Lys 10444722:46:2258
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PMID: 10456926 [PubMed] Parad RB et al: "Pulmonary outcome in cystic fibrosis is influenced primarily by mucoid Pseudomonas aeruginosa infection and immune status and only modestly by genotype."
No. Sentence Comment
51 Genomic DNA isolated from each subject was evaluated for the presence of any of twelve CFTR gene mutations (⌬F508, G551D, G542X, 621ϩ1G3T, ⌬I507, 1717-1 G3A, R117H, N1303K, W1282X, R560T, R553X, and 3849ϩ10kb C3T) by one of three standard assays (10, 11, 32).
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ABCC7 p.Asn1303Lys 10456926:51:185
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101 Of these 12, 9 had one ⌬F508 CFTR gene allele, but the second allele was identified for only 2 of these 9 subjects (N1303K and G542X); the remaining 7 subjects carried a second CFTR gene allele that was not among the 12 most common ones we screened for.
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ABCC7 p.Asn1303Lys 10456926:101:123
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118 with overall opsonic antibody titer of Ն5 26 14 Ͻ0.001 a Distribution of non-⌬F508 CFTR gene alleles in the uninfected group: G542X, 3 alleles; G551D, 1 allele; W1282X, 1 allele; N1303K, 1 allele; and not identified, 14 alleles.
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ABCC7 p.Asn1303Lys 10456926:118:198
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PMID: 10466626 [PubMed] Biffi A et al: "Restoration of bacterial killing activity of human respiratory cystic fibrosis cells through cationic vector-mediated cystic fibrosis transmembrane conductance regulator gene transfer."
No. Sentence Comment
30 The genotypes of CF polyps were D F508/D F508 (n 5 1), D F508/1717-1G R A (n 5 1), D F508/N1303K (n 5 2), and D F508/unknown (n 5 1).
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ABCC7 p.Asn1303Lys 10466626:30:90
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PMID: 10605524 [PubMed] Banjar H et al: "Geographic distribution of cystic fibrosis transmembrane regulator gene mutations in Saudi Arabia."
No. Sentence Comment
31 1 Sa S 1 1 N1303K/3120 1 1G® A* 1 NonSa W 1 1 R553X/31201 1G ® A* 1 NonSa W 1 1 7 Total 9 Total 9 Total Exon 19 I1234V 4/1/1 Sa C/W/S 12 13 NP Exon 21 N1303K/3120 1 1G® A* 1 NonSa W 1 1 N1303K/1548delG* 1 Sa E 1 1 2 Total 2 Total 2 Total a All mutations are homozygous except if otherwise indicated; ?
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ABCC7 p.Asn1303Lys 10605524:31:11
status: NEW
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ABCC7 p.Asn1303Lys 10605524:31:161
status: NEW
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ABCC7 p.Asn1303Lys 10605524:31:201
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40 CFTR mutations identi® ed 4± 11 Severe pancreatic insuf® ciency and lung disease were found in the following CFTR mutations: 1548delG was found in eight families (15% of total alleles), all native Saudis, four families from Central Province; D F508 was found in ® ve families (10%), three of non-Saudi origin from different provinces; 3120 1 1G ® A was found in seven families (9%), three being native Saudi from Eastern Province; H139L was found in three (7%) native Saudi families mainly from Eastern Province; N1303K occurred in two (2%) families and G115X in one family, 425del42, L1177X and 711 1 1G ® A were each found in one family.
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ABCC7 p.Asn1303Lys 10605524:40:540
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PMID: 10627945 [PubMed] Gundry CN et al: "Rapid F508del and F508C assay using fluorescent hybridization probes."
No. Sentence Comment
149 Other clinically significant mutations (e.g., G542X, R553X, R1162X, N1303K, W1282X, G551D, G5151X, etc.)
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ABCC7 p.Asn1303Lys 10627945:149:68
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PMID: 10733236 [PubMed] Zebrak J et al: "Partial CFTR genotyping and characterisation of cystic fibrosis patients with myocardial fibrosis and necrosis."
No. Sentence Comment
6 In this group of patients, 5 were DF508 homozygotes, 1 was DF508/ N1303K and 1 was a DF508/M compound heterozygote.
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ABCC7 p.Asn1303Lys 10733236:6:66
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8 The co-existence of a genetic predisposition to myocardial lesions resulting most probably from severe cystic fibrosis transmembrane (CFTR) genotypes (such as DF508/DF508, DF508/N1303K) and deficiency of certain trophic factors necessary for metabolism of the myocardium, are postulated to cause myocardial complications in CF leading to circulatory failure and early death.
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ABCC7 p.Asn1303Lys 10733236:8:178
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58 Of 18 deceased CF patients 5 were DF508 homozygotes, 1 was a compound heterozygote DF508/N1303K and 1 was a compound heterozygote DF508/M (M - unidentified mutation).
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ABCC7 p.Asn1303Lys 10733236:58:89
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59 The latter was negative for 14 other mutations: DI507, 1717-1G“A, G542X, G551D, R553X, R560T, 3849+10kbC“T, N1303K, W1282X, S549I, S549N, 621+1G“T, 2789+5G“A, R117H.
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ABCC7 p.Asn1303Lys 10733236:59:118
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78 No correlation of myocardial complications with CFTR mutations has been performed so far and, in the literature, only one case was recognised as a DF508/M compound heterozygote, negative for R347P, G551D, R553X and N1303K as a second mutation (9).
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ABCC7 p.Asn1303Lys 10733236:78:215
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79 In our series 5 patients were DF508 homozygotes, 1 a DF508/N1303K and 1 a DF508/ M compound heterozygote.
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ABCC7 p.Asn1303Lys 10733236:79:59
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82 N1303K mutation was also classified as 'severe`, at least with regard to pancreatic involvement (29).
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ABCC7 p.Asn1303Lys 10733236:82:0
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95 This conclusion does not negate previous hypotheses: we rather postulate a co-existence of genetic predisposition to myocardial lesions resulting mainly from CFTR genotypes such as DF508/DF508 and DF508/N1303K which are considered 'severe`, and/ or the presence of certain modifier genes together with a deficiency of certain trophic factors necessary for myocardial metabolism.
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ABCC7 p.Asn1303Lys 10733236:95:203
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172 Osborne L, Santis G, Schwarz M et al. Incidence and expression of the N1303K mutation of the cystic fibrosis (CFTR) gene.
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ABCC7 p.Asn1303Lys 10733236:172:70
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PMID: 10746558 [PubMed] Bombieri C et al: "A new approach for identifying non-pathogenic mutations. An analysis of the cystic fibrosis transmembrane regulator gene in normal individuals."
No. Sentence Comment
79 Out of the 20 missense mutations, three (G85E, ∆F508, and N1303K) are certainly CF-causing, and several (R31C, K68E, R75Q, I148T, V562L, G576A-R668C, L997F, F1052V, S1235R) have been described in congenital bilateral absence of the vas deferens, in disseminated bronchiectasis, in pancreatitis, or in atypical CF cases mutations as reported in the CFGAC website ().
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ABCC7 p.Asn1303Lys 10746558:79:65
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80 Many (13 out of 20) of the missense mutations change highly conserved (5/5 species analyzed) amino acid residues (R75Q, G85E, I148T, I506V, R668C, G622D, L997F, I1027T, F1052V, L1096R, I1131V, R1162L, N1303K); others affect amino acid residues conserved in 4/5 species (K68 E, R170H, M470V, V562L, S1235R), or in 3/5 species (R31C and G576A; Tucker et al. 1992).
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ABCC7 p.Asn1303Lys 10746558:80:201
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88 In three further cases where more than one sporadic mutation was observed in the same individual (1341+28 C/T and F1052V and S1235R; ∆F508 and I1027T; 1716G/A and N1303K), data from the literature were not available, and segregation analysis was not possible; thus, their phase could not be established.
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ABCC7 p.Asn1303Lys 10746558:88:170
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91 The remaining 30 (after having excluded the certainly CF-causing mutations G85E, ∆F508 and N1303K) have been found a few times only: once (20 mutations), twice (five mutations), three times (three mutations), four times (one mutation), and eight times (one mutation).
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ABCC7 p.Asn1303Lys 10746558:91:98
status: NEW
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PMID: 10755189 [PubMed] Stuhrmann M et al: "CFTR gene mutations and male infertility."
No. Sentence Comment
95 Most patients are of German origin CFTR genotype (mutation class in brackets) Patients with typical CF (%) Patients with CBAVD (%) DF508 (2)/DF508 (2) 247 (59.4) 0 DF508 (2)/N1303K (2) 17 (4.1) 0 DF508 (2)/R347P (4) 13 (3.1) 0 DF508 (2)/R553X (1) 11 (2.6) 0 DF508 (2)/G542X (1) 11 (2.6) 0 DF508 (2)/G551D (3) 11 (2.6) 0 DF508 (2)/R1162X (1) 10 (2.4) 0 DF508 (2)/3849+10 KbC T (5) 9 (2.2) 0 DF508 (2)/2789+5G A (5) 9 (2.2) 0 DF508 (2)/3272-26 A G (5) 7 (1.7) 2 (2.6) DF508 (2)/1717-1G A (1) 6 (1.4) 0 DF508 (2)/CFTRdel21Kb (1) 5 (1.2) 0 DF508 (2)/R117H (4) 3 (0.7) 21 (26.9)* DF508 (2)/IVS8-5T (5) 2 (0.5) 9 (11.5)* DF508 (2)/other 33 (7.9) 20 (25.6) Other/other 22 (5.3) 26 (33.3) *Including one CUAVD patient each.
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ABCC7 p.Asn1303Lys 10755189:95:174
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122 In this subgroup, eight out of nine patients In summary, CFTR mutations are the molecu- had one of the following mutations detected on lar cause for a variety of different forms of male one of their two CFTR alleles: DF508 (n=4), infertility due to obstructive azoospermia, ranging R117H (n=2), G551D (n=1) and N1303K (n=1) from CBAVD and CUAVD with contralateral (Mickle et al., 1995).
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ABCC7 p.Asn1303Lys 10755189:122:311
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PMID: 10777364 [PubMed] Wang J et al: "A novel mutation in the CFTR gene correlates with severe clinical phenotype in seven Hispanic patients."
No. Sentence Comment
320 Since ATP hydrolysis at NBD2 terminates a burst of activities associated with opening the channel, loss of NBD2 would confer a loss of the gating control.21 A recent study shows that the Walker A motif in NBD2 is more solvent accessible than that in NBD1, suggesting a diVerence in structure and function for the two NBDs.22 In addition to 3876delA, a few other mutations in NBD2, including G1244E, S1255P, S1255X, 3905insT, W1282X, N1303K, and G1349D, all result in a PI phenotype.5 23 It should be noted that S1255P, S1255X, 3905insT, and 3876delA are all clustered around the Walker A motif.
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ABCC7 p.Asn1303Lys 10777364:320:433
status: NEW
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570 SYLVAIN R RIVARD* CHRISTIAN ALLARD† JEAN-PIERRE LEBLANC† MARCEL MILOT† GERVAIS AUBIN† FERNAND SIMARD† CLAUDE FÉREC‡ MARC DE BRAEKELEER†§¶ *Département des Sciences Fondamentales, Université du Québec à Chicoutimi, Canada Table 1 Distribution of cystic fibrosis patients diagnosed before the age of 5 by age groups in Saguenay-Lac-Saint-Jean, (A) by genotype, (B) by mutation 0-10 years 10.1-20 years Over 20 years All ages No % No % No % No % (A) Genotype F508/ F508 15 (1) 40.5 21 (2) 36.2 18 (3) 42.9 54 (6) 39.4 F508/621+1G→T 12 (1) 32.4 16 (1) 27.6 10 (1*) 23.8 38 (3*) 27.7 F508/A455E 1 2.7 6 10.3 5 11.9 12 8.8 F508/I148T 1 2.7 1 1.7 2 1.5 F508/Y1092X 3 (1) 5.2 1 2.4 4 (1) 2.9 F508/Q890X 1 2.4 1 0.7 F508/R1158X 1 2.4 1 0.7 621+1G→T/621+1G→T 2 (1) 5.4 4 6.9 1 2.4 7 (1) 5.1 621+1G→T/A455E 1 2.7 4 6.9 3 7.1 8 5.8 621+1G→T/711+1G→T 2 (1) 5.4 2 (1) 3.4 4 (2) 2.9 621+1G→T/Y1092X 1 2.7 1 0.7 621+1G→T/S489X 1 2.7 1 0.7 621+1G→T/G85E 1 (1) 1.7 1 (1) 2.4 2 (2) 1.5 A455E/R117C 1 2.7 1 0.7 N1303K/I148T 1 2.4 1 0.7 Total 37 58 42 137 Death (4) 10.8 (6) 10.3 (5*) 11.9 (15*) 10.9 (B) Mutation F508 16 (1) 43.2 25 (3) 43.1 21 (3) 51.2 62 (7) 45.6 621+1G→T 18 (3) 48.6 23 (3) 39.7 12 (2*) 29.3 53 (8*) 39.0 A455E 3 8.1 10 17.2 8 19.5 21 15.4 Total 37 58 41 136 Death (4) 10.8 (6) 10.3 (5*) (12.2) (15*) (11.0) ( ): Number of deaths.
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ABCC7 p.Asn1303Lys 10777364:570:1138
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PMID: 10777368 [PubMed] Rivard SR et al: "Correlation between mutations and age in cystic fibrosis in a French Canadian population."
No. Sentence Comment
320 Since ATP hydrolysis at NBD2 terminates a burst of activities associated with opening the channel, loss of NBD2 would confer a loss of the gating control.21 A recent study shows that the Walker A motif in NBD2 is more solvent accessible than that in NBD1, suggesting a diVerence in structure and function for the two NBDs.22 In addition to 3876delA, a few other mutations in NBD2, including G1244E, S1255P, S1255X, 3905insT, W1282X, N1303K, and G1349D, all result in a PI phenotype.5 23 It should be noted that S1255P, S1255X, 3905insT, and 3876delA are all clustered around the Walker A motif.
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ABCC7 p.Asn1303Lys 10777368:320:433
status: NEW
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570 SYLVAIN R RIVARD* CHRISTIAN ALLARD† JEAN-PIERRE LEBLANC† MARCEL MILOT† GERVAIS AUBIN† FERNAND SIMARD† CLAUDE FÉREC‡ MARC DE BRAEKELEER†§¶ *Département des Sciences Fondamentales, Université du Québec à Chicoutimi, Canada Table 1 Distribution of cystic fibrosis patients diagnosed before the age of 5 by age groups in Saguenay-Lac-Saint-Jean, (A) by genotype, (B) by mutation 0-10 years 10.1-20 years Over 20 years All ages No % No % No % No % (A) Genotype F508/ F508 15 (1) 40.5 21 (2) 36.2 18 (3) 42.9 54 (6) 39.4 F508/621+1G→T 12 (1) 32.4 16 (1) 27.6 10 (1*) 23.8 38 (3*) 27.7 F508/A455E 1 2.7 6 10.3 5 11.9 12 8.8 F508/I148T 1 2.7 1 1.7 2 1.5 F508/Y1092X 3 (1) 5.2 1 2.4 4 (1) 2.9 F508/Q890X 1 2.4 1 0.7 F508/R1158X 1 2.4 1 0.7 621+1G→T/621+1G→T 2 (1) 5.4 4 6.9 1 2.4 7 (1) 5.1 621+1G→T/A455E 1 2.7 4 6.9 3 7.1 8 5.8 621+1G→T/711+1G→T 2 (1) 5.4 2 (1) 3.4 4 (2) 2.9 621+1G→T/Y1092X 1 2.7 1 0.7 621+1G→T/S489X 1 2.7 1 0.7 621+1G→T/G85E 1 (1) 1.7 1 (1) 2.4 2 (2) 1.5 A455E/R117C 1 2.7 1 0.7 N1303K/I148T 1 2.4 1 0.7 Total 37 58 42 137 Death (4) 10.8 (6) 10.3 (5*) 11.9 (15*) 10.9 (B) Mutation F508 16 (1) 43.2 25 (3) 43.1 21 (3) 51.2 62 (7) 45.6 621+1G→T 18 (3) 48.6 23 (3) 39.7 12 (2*) 29.3 53 (8*) 39.0 A455E 3 8.1 10 17.2 8 19.5 21 15.4 Total 37 58 41 136 Death (4) 10.8 (6) 10.3 (5*) (12.2) (15*) (11.0) ( ): Number of deaths.
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ABCC7 p.Asn1303Lys 10777368:570:1138
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PMID: 10794365 [PubMed] Bernardino AL et al: "Molecular analysis in Brazilian cystic fibrosis patients reveals five novel mutations."
No. Sentence Comment
6 Another fifteen mutations (previously reported) were detected: G542X, R1162X, N1303K, R334W, W1282X, G58E, L206W, R553X, 6211 1GRT, V232D, 1717-1GRA, 2347 delG, R851L, 27891 5GRA, and W1089X.
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ABCC7 p.Asn1303Lys 10794365:6:78
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51 The next most common mutations were: G542X (8.8%), R1162X (2.5%), N1303K (2.5%), R334W (2.5%), W1282X (1.3%), G58E (1.3%), L206W (0.6%), and R553X (0.6%).
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ABCC7 p.Asn1303Lys 10794365:51:66
status: NEW
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81 In this study, 16 mutations were identified: D F508, G542X, R1162X, N1303K, R334W, W1282X, G58E, L206W, R553X, 6211 1GRT, V232D, 1717-1GRA, 2347 delG, R851L, 27891 5GRA, and W1089X.
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ABCC7 p.Asn1303Lys 10794365:81:68
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84 GEN OTYPES, FREQUENCIES, AN D PRESENCE OF PI FRO M 160 CF PATIE NTS (320 CF CHROM OSOM ES) Number and frequency (%) Genotype Number Frequency (%) of patients with PI D F508/D F508 47 29.40 47 (100%) D F508/G542X 13 8.10 13 (100%) D F508/R1162X 6 3.80 6 (100%) D F508/R334W 5 3.10 3 (60%) D F508/N1303K 3 1.90 3 (100%) D F508/W1282X 2 1.20 2 (100%) D F508/G58E 2 1.20 1 (50%) D F508/L206W 1 0.62 0 D F508/R553X 1 0.62 1 (100%) D F508/R851L 1 0.62 0 D F508/2789 1 5g ® A 1 0.62 0 D F508/3617delGA 1 0.62 1 (100%) D F508/3171delC 1 0.62 1 (100%) D F508/2686insT 1 0.62 1 (100%) D F508/Y275X 1 0.62 1 (100%) D F508/U 22 13.80 14 (64%) G542X/G542X 3 1.90 3 (100%) G542X/N1303K 3 1.90 2 (67%) G542X/R1162X 1 0.62 1 (100%) G542X/U 5 3.10 4 (80%) N1303K/R1162X 1 0.62 1 (100%) N1303K/G58E 1 0.62 0 2347delG/2347delG 1 0.62 1 (100%) R334W/V232D 1 0.62 0 R334W/W1089X 1 0.62 1 (100%) R334W/U 1 0.62 1 (100%) W1282X/U 1 0.62 1 (100%) G58E/U 1 0.62 1 (100%) R553X/U 1 0.62 1 (100%) L206W/U 1 0.62 0 621 1 1G ® T/U 1 0.62 1 (100%) 1717-1G ® A/U 1 0.62 Not known V201M/U 1 0.62 0 U/U 27 16.90 12 (44%) Total 160 100 - U, Unknown CF mutation.
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ABCC7 p.Asn1303Lys 10794365:84:295
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ABCC7 p.Asn1303Lys 10794365:84:670
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ABCC7 p.Asn1303Lys 10794365:84:744
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ABCC7 p.Asn1303Lys 10794365:84:774
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89 Two other mutations-N1303K (2.5%) and R1162X (2.5%)-were also found in frequencies compatible with the ethnic origins of our Caucasian population.
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ABCC7 p.Asn1303Lys 10794365:89:20
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90 The N1303K mutation has been reported in Southern Europeans as the fourth most common mutation, with a frequency of 3.2% (Nunes et al., 1991), and the R1162X mutation is the second most frequent mutation in Northern Italy (about 10%) (Casals et al., 1993).
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ABCC7 p.Asn1303Lys 10794365:90:4
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104 However, one of our compound heterozygote patients for severe mutations (N1303K/G542X), has PS.
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ABCC7 p.Asn1303Lys 10794365:104:73
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110 Unexpectedly, however one compound heterozygote (N1303K/G542X) CF patients (who was referred to above as having PS) was the son of first cousins, which is compatible with the high frequency of CFTR heterozygotes in the population.
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ABCC7 p.Asn1303Lys 10794365:110:49
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PMID: 10798368 [PubMed] Orozco L et al: "Spectrum of CFTR mutations in Mexican cystic fibrosis patients: identification of five novel mutations (W1098C, 846delT, P750L, 4160insGGGG and 297-1G-->A)."
No. Sentence Comment
27 Detection of known mutations ∆F508, G542X, N1303K, ∆I507 and 2869insG were screened by PCR-mediated site directed mutagenesis (PSM) as previously described (Friedman et al. 1991).
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ABCC7 p.Asn1303Lys 10798368:27:50
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41 The second most common mutation was G542X, present in 6.1% of CF chromosomes, followed by ∆I507 and S549N (each 2.5%), N1303K (2.06%) and 2055del→A (1.03%).
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ABCC7 p.Asn1303Lys 10798368:41:126
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69 First, we tested these patients for 12 mutations selected for the following reasons: five are the most common mutations worldwide (∆F508, G542X, N1303K, G551D and R553X; CFGAC 1994); 362 Table 1 Frequency of the CFTR gene mutations in 97 (194 chromosomes) Mexican patients Mutation Number of Frequency affected alleles (%) ∆F508 79 40.72 G542X 12 6.18 ∆I507 5 2.57 S549N 5 2.57 N1303K 4 2.06 R75X 3 1.54 406-1G→A 3 1.54 I148T 3 1.54 2055del9→A 2 1.03 935delA 2 1.03 I506T 2 1.03 3199del6 2 1.03 2183AA→G 2 1.03 G551D 1 0.51 R553X 1 0.51 1924del7 1 0.51 G551S 1 0.51 1078delT 1 0.51 Y1092X 1 0.51 R117H 1 0.51 G85E 1 0.51 3849+10KbC→T 1 0.51 1716G→A 1 0.51 W1204X 1 0.51 W1098Ca 1 0.51 846delTa 1 0.51 P750La 1 0.51 V754M 1 0.51 R75Q 1 0.51 W1069X 1 0.51 L558S 1 0.51 4160insGGGGa 1 0.51 297-1G→Aa 1 0.51 H199Y 1 0.51 2869insG 0 0 R1162X 0 0 3120+1G→A 0 0 Total 34 145 74.58% aNovel mutations detected in this study Fig.1 Sequencing ladders showing the CFTR novel mutations.
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ABCC7 p.Asn1303Lys 10798368:69:152
status: NEW
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ABCC7 p.Asn1303Lys 10798368:69:399
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PMID: 10834512 [PubMed] Kambouris M et al: "Identification of novel mutations in Arabs with cystic fibrosis and their impact on the cystic fibrosis transmembrane regulator mutation detection rate in Arab populations."
No. Sentence Comment
0 ORIGINAL PAPER M. Kambouris á H. Banjar á I. Moggari á H. Nazer á M. Al-Hamed á B. F. Meyer Identi®cation of novel mutations in Arabs with cystic ®brosis and their impact on the cystic ®brosis transmembrane regulator mutation detection rate in Arab populations Received: 18 December 1998 / Accepted: 14 May 1999 Abstract The cystic ®brosis transmembrane regulator (CFTR) gene in Arab patients with cystic ®brosis (CF) (sweat chloride >60 mmol/l) from 61 unrelated families was screened for mutations in exons 3, 4, 5, 7, 10, 11, 16 and 19 and for mutations W1282X, N1303K and 3849 + 10kbC ® T.
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ABCC7 p.Asn1303Lys 10834512:0:615
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43 Mutation analysis All patients were screened for known mutations 3849 + 10KbC ® T (intron 19), W1282X (exon 20) and N1303K (exon 21) by restriction enzyme digestion analysis with enzymes Mnl I, Bst OI and Hph I respectively according to standard protocols [23].
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ABCC7 p.Asn1303Lys 10834512:43:121
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63 Of more than 850 known CFTR mutations (http:// www.genet.sickkids.on.ca/cftr-cgi-bin/Mutation Table), only 9 were encountered in this study: R75X, A141D, 1249G ® A, DF508, S549R, R553X, 3120 + 1G ® A, I1234V and N1303K.
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ABCC7 p.Asn1303Lys 10834512:63:222
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93 In that study, three mutations, DF508 (37.5%), W1282X (15.6%), and N1303K (9.4%) collectively accounted for 62.5% of the CF alleles.
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ABCC7 p.Asn1303Lys 10834512:93:67
status: NEW
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100 This is highlighted by the absence of families with the DF508 mutation which is present in 13% of our study group including Saudi Arabs. The study lists only three common mutations among Arab: the ®rst (3120 + 1A ® G) was found in three families while the other two (N1303K and 1548delG), in only two families.
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ABCC7 p.Asn1303Lys 10834512:100:277
status: NEW
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111 1 (private mutation) Exon 10 1548delG Frame shift 8 16 Altered residues at aa 473; stop codon at 526 1a [R75X] 1 1a [1811 + 2 T ® C] 1 1a [N1303K] 1 2a [?]
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ABCC7 p.Asn1303Lys 10834512:111:144
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114 1 (private mutation) 1779T ® G S549R 1 2 1a [H139L] 1 Total: 2 2.5% 1789C ® T R553X ± protein truncation 1a [3120 + 1G ® A] 1 (private mutation) 1811 + 2T ® C Splice site 1a [1548delG] 1 (private mutation) Exon 16 3120 + 1G ® A Splice site 5 10 1a [R533X] 1 1a [N1303K] 1 1a [?]
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ABCC7 p.Asn1303Lys 10834512:114:292
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115 1 Total: 8 11% Exon 19 3661A ® T K1177X ± protein truncation 1 2 (private mutation) 3832A ® G I1234V 7 14 1a [G115X] 1 Total: 8 12.5% Exon 21 4041C ® G N1303K 1a [1548delG] 1 1a [3120 + 1G ® A] 1 Total: 2 1.5% Undetected 11 22 1a [425del42] 1 1a [711 + 1G ® A] 1 2a [1548delG] 2 2a [DF508] 2 1a [F533L] 1 1a [1249 + 1G ® A] 1 1a [3120 + 1G ® A] 1 Total: 20 25% a Indicates a compound heterozygous family.
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ABCC7 p.Asn1303Lys 10834512:115:172
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PMID: 10875853 [PubMed] Casals T et al: "Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens."
No. Sentence Comment
104 In a small group of G85E/- 7T/7T 1 patients, alpha-glucosidase activity was 18.5 Ϯ 2.7 mU/ml in 2752-15C→G/- 7T/7T 1 CUAVD (n ϭ 4), and 26.7 Ϯ 5.5 mU/ml in CBAVD (n ϭ 7).L997F/-a 7T/7T 1 1677delTA/- 7T/7T 1 After reclassification of the patients according to the presence Y1014C/- 7T/9T 1 of zero, one or two mutations, none of the variables showed N1303K/- 7T/9T 1 significant differences either in CUAVD or CBAVD (notNegative CFTR mutation 16 (15) -/- 7T/7T 12 (11) shown).
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ABCC7 p.Asn1303Lys 10875853:104:380
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PMID: 10922395 [PubMed] Abramowicz MJ et al: "Fetal bowel hyperechogenicity may indicate mild atypical cystic fibrosis: a case associated with a complex CFTR allele."
No. Sentence Comment
14 The N1303K mutation was found in the fetus and the father and no mutation was found on the maternal allele or in the mother.
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ABCC7 p.Asn1303Lys 10922395:14:4
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17 The routine DNA analysis showed the presence of the paternal N1303K mutation in both the younger and the older brother.
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ABCC7 p.Asn1303Lys 10922395:17:61
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25 The two brothers and fetus are compound heterozygotes for the N1303K mutation and the complex CFTR allele D443Y-G576A-R668C.
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ABCC7 p.Asn1303Lys 10922395:25:62
status: NEW
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29 N1303K N D443Y G576A R668C N D443Y G576A R668C N1303K D443Y G576A R668C N1303K D443Y G576A R668C N1303K Electronic letter of 3 www.jmedgenet.com a regular basis and propose the following approach.
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ABCC7 p.Asn1303Lys 10922395:29:0
status: NEW
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ABCC7 p.Asn1303Lys 10922395:29:47
status: NEW
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ABCC7 p.Asn1303Lys 10922395:29:72
status: NEW
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ABCC7 p.Asn1303Lys 10922395:29:97
status: NEW
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PMID: 10922396 [PubMed] Teder M et al: "Distribution of CFTR gene mutations in cystic fibrosis patients from Estonia."
No. Sentence Comment
7 First, several known mutations were tested directly by the heteroduplex analysis (HA; F508, 394delTT, polyT variants in IVS8), restriction digestion (RD; G551D, R553X, 1811+1.6kbA→G, L206W, 3849+10kbC→T), and amplification refractory mutation system (ARMS, kits from Cellmark Diagnostics, UK; G542X, 621+1G→T, N1303K).
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ABCC7 p.Asn1303Lys 10922396:7:331
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66 This is the second most frequent mutation in several Nordic populations, with a relative frequency of 1.9% in Denmark,2 3.2% in Flanders,32 6.5% in Sweden,2 2.2-5.5% in Norway,2 and 30% in Finland.3 It was also found on 1.5% of the CF chromosomes in Russia.32 We did not find any of the mutations more common in European populations, such as G542X (2.6%), N1303K (1.6%), G551D (1.5%), or W1282X (1.0%),4 which is not surprising, as the relative frequency of these mutations is less than 1% in Nordic countries also.
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ABCC7 p.Asn1303Lys 10922396:66:356
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PMID: 10923221 [PubMed] Dawson KP et al: "The geographic distribution of cystic fibrosis mutations gives clues about population origins."
No. Sentence Comment
12 Eur J Pediatr (2000) 159: 496±499 Ó Springer-Verlag 2000 K. P. Dawson (&) Department of Paediatrics, Faculty of Medicine and Health Sciences, UAE University, PO Box 17666, Al Ain, United Arab Emirates P. M. Frossard Department of Pathology, Faculty of Medicine and Health Sciences, UAE University, PO Box 17666, Al Ain, United Arab Emirates We present here population genetics data that has been gathered about the DF508 mutation and information with regards to two other common mutations, namely G542X and N1303K.
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ABCC7 p.Asn1303Lys 10923221:12:518
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58 The frequency of the N1303K allele varies signi®cantly between countries and ethnic groups.
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ABCC7 p.Asn1303Lys 10923221:58:21
status: NEW
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113 Osborne L, Santis G, Schwarz M, Osborne L, Santis G, Schwarz M, Klinger K, DoÈ rk T, McIntosh I, Schwartz M, Nunes V, Macek Jr. M, Reiss J, Highsmith Jr. WE, McMahon R, Novelli G, Malik N, BuÈ rger J, Anvret M, Wallace A, Williams C, Mathew C, Rozen R, Graham C, Gasparini P, Bal J, Cassiman JJ, Balassopoulou A, Davidow L, Raskin S, Kalaydjieva L, Kerem B, Richards S, Simon-Bouy B, Super M, Wulbrand U, Keston M, Estivill X, Vavrova V, Friedman KJ, Barton D, Dallapiccola B, Stuhrmann M, Beards F, Hill AJM, Pignatti PF, Cuppens H, Angelicheva D, TuÈ mmler B, Brock DJH, Casals T, Macek M, Schmidtke J, Magee AC, Bonizzato A, DeBoeck C, Ku€ardjieva A, Hodson M, Knight RA (1992) Incidence and expression of the N1303K mutation of the cystic ®brosis (CFTR) gene.
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ABCC7 p.Asn1303Lys 10923221:113:733
status: NEW
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PMID: 10933918 [PubMed] Noone PG et al: "Safety and biological efficacy of a lipid-CFTR complex for gene transfer in the nasal epithelium of adult patients with cystic fibrosis."
No. Sentence Comment
55 A nasal scrape biopsy was done TABLE 1 Study Subjects Who Completed the Protocol Subject Age (years) Gender Genotype FEV1 (% pred)a 1 19 Male ⌬F 508/2183delAA-G 101 2 37 Female ⌬F 508/⌬F 508 48 3 35 Female ⌬F 508/⌬F 508 74 4 24 Male ⌬F 508/711 ϩ 1 G Ͼ T 69 5 19 Male ⌬F 508/2183delAA-G 103 6 43 Female ⌬F 508/⌬F 508 55 7 48 Male ⌬F 508/N1303K 48 8 26 Female ⌬F 508/⌬F 508 80 9 28 Male ⌬F 508/⌬F 508 53 10 29 Female ⌬F 508/⌬F 508 42 11 37 Female ⌬F 508/unknown 115 a Subjects were required to have an FEV1 greater than 40% predicted, basal PD Ͼ -30 mV, with absent CFTR-mediated Cl- con- ductance. on days 3 (along the medial surface of the inferior turbinate) and 5 (under the inferior turbinate) and optionally on days 9 Ϯ 2 and 28 Ϯ 2.
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ABCC7 p.Asn1303Lys 10933918:55:418
status: NEW
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PMID: 10940786 [PubMed] Zeitlin PL et al: "Future pharmacological treatment of cystic fibrosis."
No. Sentence Comment
22 Examples of CFTR mutations organized by classification of the defect in CFTR biosynthesis Type Genotype Phenotype Defect Cell diagram Drugs that may improve phenotype G542X 621+1 G → T 3905insT W1282X R553X 1717-1 G → A PI no CFTR protein no cell surface chloride transport gentamicin G418 Class II [64] 'F508 N1303K (P574H)a (A455E)a PI defective CFTR processing defective CFTR trafficking no cell surface chloride transport chemical chaperones CPX phenylbutyrate deoxyspergualin Class III [64] G551D G551S PI defective chloride channel regulation reduced or absent cell surface chloride transport genistein pyrophosphate Class IV [64, 66] R117H R334W G314E R347P ('F508)a P574H PS reduced chloride conductance reduced levels of cell surface chloride transport genistein milrinone phenylbutyrate Class V [64] 3849+10 kb C → T 2789+5 G → A 3272-26 A → G A455E 3120+1 G → A 1811+1.6 kb A → G 5Tb PS normal CFTR channels reduced numbers of normal CFTR reduced cell surface chloride transport genistein milrinone phenylbutyrate a Some mutants have features of more than one class of defect.
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ABCC7 p.Asn1303Lys 10940786:22:324
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PMID: 10950058 [PubMed] Ockenga J et al: "Mutations of the cystic fibrosis gene, but not cationic trypsinogen gene, are associated with recurrent or chronic idiopathic pancreatitis."
No. Sentence Comment
53 Using the ARMS technology (elucigene CF20, Zeneca Diagnostics, Oxfordshire, UK) all samples were tested additionally for the mutations E60X, R347P, A455E, 1078delT, 2183AA3G, G542X, G551D, N1303K, W1282X, 1717-1G3A, R553X, 621ϩ1G3T, R117H, R1162X, 3849ϩ10kbC3T, R334W, S1251N, and 3659delC.
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ABCC7 p.Asn1303Lys 10950058:53:189
status: NEW
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PMID: 10952679 [PubMed] Mall M et al: "Effect of genistein on native epithelial tissue from normal individuals and CF patients and on ion channels expressed in Xenopus oocytes."
No. Sentence Comment
26 Eight CF patients presenting with nasal polyps were tested for six common mutations: DF508, R553X, N1303K, G542X, G551D and R347P.
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ABCC7 p.Asn1303Lys 10952679:26:99
status: NEW
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30 In all CF patients from whom rectal biopsies were studied DNA analysis was carried out for the following CFTR mutations: DF508; R117H and S108F in exon 4; R347P, R347H, I336K and T338I in exon 7; S549N, G551D, R553X, G542X, Q552X, 1717-1 G?A in exon 11; W1282X and 3905insT in exon 20; N1303K in exon 21 and 3849+10kB C?T in intron 19.
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ABCC7 p.Asn1303Lys 10952679:30:286
status: NEW
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31 Screening for these mutations identi®ed the genotypes as follows: DF508/DF508 (n=2); DF508/R553X (n=3); DF508/N1303K (n=1); DF508/3905insT (n=1); DF508/7(n=5) (7=mutation not identi®ed).
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ABCC7 p.Asn1303Lys 10952679:31:115
status: NEW
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224 In the present study we examined the e€ect of genistein on tissues derived from CF patients carrying DF508 CFTR on at least one allele and some patients were shown to be compound heterozygous with a second severe mutation (R553X, N1303K, 3905insT, G551D).
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ABCC7 p.Asn1303Lys 10952679:224:235
status: NEW
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PMID: 10973878 [PubMed] Costes B et al: "Prenatal detection by real-time quantitative PCR and characterization of a new CFTR deletion, 3600+15kbdel5.3kb (or CFTRdele19)."
No. Sentence Comment
51 The mutations tested were S549N, S549R, R553X, G551D, V520F, ⌬I507, ⌬F508, Q493X, 1717-1G3A, G542X, R560T, R347P, R347H, 3849ϩ4A3G, W1282X, R334W, 1078delT, 3849ϩ10kbC3T, R1162X, N1303K, 3659delC, 3905insT, A455E, R117H, Y122X, 2183AA3G, 2789ϩ5G3A, 1898ϩ1G3A, 621ϩ1G3T, 711ϩ1G3T, and G85E.
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ABCC7 p.Asn1303Lys 10973878:51:205
status: NEW
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PMID: 10980944 [PubMed] Bornstein JD et al: "Cystic fibrosis in the pancreas: recent advances provide new insights."
No. Sentence Comment
99 Genotypes of Seven ICP Patients with CFTR mutations Patient Gender Mutations Intron 8 Age at onset, y ICP # Days hospitalized ERCP class 1 Male ⌬F508/R117H 9T/7T 45 11 46 Moderate 2 Female ⌬F508/wt 9T/5T 32 7 52 Moderate 3 Female ⌬F508/wt 9T/5T 48 20 100+ Moderate 4 Female ⌬F508/wt 9T/7T 40 25 100+ Moderate 5 Female ⌬F508/wt 9T/7T 15 16 62 Mild 6 Female R117H/wm 7T/7T 32 6 60 Moderate 7 Male N1303K/wt 7T/9T 43 1 6 Moderate ERCP-endoscopic retrograde cholangiopancreatography; ICP-idiopathic chronic pancreatitis.
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ABCC7 p.Asn1303Lys 10980944:99:430
status: NEW
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PMID: 11000267 [PubMed] Thelwell N et al: "Mode of action and application of Scorpion primers to mutation detection."
No. Sentence Comment
39 We have used Scorpion primers to detect five common ABCC7 mutations, ∆F508 (11-13), N1303K (15), W1282X (12), G542X (12) and G551D (12,16) (Table 1).
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ABCC7 p.Asn1303Lys 11000267:39:91
status: NEW
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60 Mutation site Base change Probe-target mismatch ∆F508 M55115 436-438 CTT del - N1303K M55128 329 C→G C-C W1282X M55127 395 G→A C-A G551D M55116 362 G→A C-A G542X M55116 334 G→T C-T All PCR reactions were carried out on a Roche LightCycler.
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ABCC7 p.Asn1303Lys 11000267:60:86
status: NEW
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72 Oligo name Code Oligo sequence MTHFR forward primer BPF 5'-CTGACCTGAAGCACTTGAAGG-3' MTHFR reverse primer BPR 5'-ATGTCGGTGCATGCCTTCAC-3' MTHFR Molecular Beacon MMB 5'-FAM GCGAGTGCGGGAGCCGATTTCTCGC MR-3' MTHFR TaqMan MT 5'-FAM TGCGGGAGCCGATTT TAMRA-3' MTHFR Scorpion MS 5'-FAM CCCGCGGAAATCGGCTCCCGCACCGCGGG MR HEG CTGACCTGAAGCACTTGAAGG-3' ∆F508 normal Scorpion 508S 5'-FAM CCGCGCAAACACCAAAGATGATATTTTCTGCGCGG MR HEG AGTTTTCCTGGATTATGCCT-3' ∆F508 mutant Scorpion 508M 5'-ROX CCGC(F)GCAAACACCAATGATATTTTCTGCAGCGG MR HEG AGTTTTCCTGGATTATGCCT-3' ∆F508 reverse primer 508R 5'-TTGGGTAGTGTGAAGGGTTC-3' ∆F508 forward primer 508F 5'-AGTTTTCCTGGATTATGCCT-3' Hybrid Scorpion HS 5'-FAM CCGCGCAAACACCAAAGATGATATTTTCTGCGCGG MR HEG CTTGGAGAAGGTGGAATCAC-3' N1303K Scorpion N13S 5'-FAM CCCGCGCGGAACATTTAGAAAAAACTTGGATCCCGCGCGGG MR HEG TTTCTTGATCACTCCACTGTTC-3' N1303K reverse primer N13R 5'-CATACTTTCTTCTTCTTTTCTTT-3' W1282X Scorpion W12S 5'-FAM CCCGCGCCTTTCCTCCACTGTTGCGCGCGGG MR HEG ATGGTGTGTCTTGGGATTCA-3' W1282X reverse primer W12R 5'-GGCTAAGTCCTTTTGCTCAC-3' G551D Scorpion 551S 5'-FAM CCCGCGCCTCGTTGACCTCCACTCGCGCGGG MR HEG CTTGGAGAAGGTGGAATCAC-3' G551D reverse primer 551R 5'-AAATGCTTGCTAGACCAATA-3' G551D forward primer 551F 5'-CTTGGAGAAGGTGGAATCAC-3' G551D-DIST Scorpion (90 bases between 3'-end of Scorpion primer and 5'-end of probe target) G90 5'-FAM CCCGCGCCTCGTTGACCTCCACTCGCGCGGG MR HEG CAGATTGAGCATACTAAAAG-3' G542X Scorpion G542S 5'-FAM CCGCGCACCTTCTCCAAGAACTAGCGCGG MR HEG CCAAGTTTGCAGAGAAAGAC-3' G542X reverse primer G542R 5'-AAATGCTTGCTAGACCAATA-3' Table 3.
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ABCC7 p.Asn1303Lys 11000267:72:767
status: NEW
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ABCC7 p.Asn1303Lys 11000267:72:870
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73 Annealing and fluorescence monitoring temperatures used for each locus Loci/test Annealing temperature (°C) Monitoring temperature (°C) ∆F508 48 51 N1303K 44 61 W1282X 49 53 G551D 47 55 G551D-DIST 46 55 G542X 48 53 Unimolecular versus bimolecular test 47 51 Distance constraints G90 Scorpion 46 55 G551DS Scorpion 47 55 MTHFR 58 58 described in Results were 95°C for 30 s, 58°C for 60 s and 72°C for 30 s.
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ABCC7 p.Asn1303Lys 11000267:73:165
status: NEW
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PMID: 11025834 [PubMed] Wang X et al: "Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population."
No. Sentence Comment
11 Results Eleven CRS patients were found to have a CF mutation (⌬F508, n=9; G542X, n=1; and N1303K, n=1).
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ABCC7 p.Asn1303Lys 11025834:11:97
status: NEW
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30 Analysis of CFTR Genes Genomic DNA samples extracted from the blood of participants were screened for 16 mutations (R117H, 621+1G→T, R334W, R347P, A455E, ⌬I507, ⌬F508, 1717-1 G→A, G542X, S549N, G551D, R553X, R560T, 3849+10 Kb C→T, W1282X, and N1303K) that account for 85% of CF alleles in the white population using the multiplex reverse dot hybridization system (Roche Molecular Systems, Alameda, Calif).16,17 This test also identified the 5T, 7T, and 9T variants of the splice acceptor site in intron 8 and F508C, I507V, and I506V (exon 10) polymorphisms of the CFTR gene.
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ABCC7 p.Asn1303Lys 11025834:30:278
status: NEW
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46 Eleven CRS patients were found to have CF mutations (TABLE 1); 9 had the common mutation, ⌬F508, 1 had G542X, and 1 had N1303K.
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ABCC7 p.Asn1303Lys 11025834:46:127
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53 Using this technique, we previously demonstrated that at least 96% of mutations in the exons and flanking intron regions of the CFTR gene can be detected.16 A 97% sensitivity was achieved using 115 samples with previously identified mutations16 in this study.Sequenceanalysisofsampleswith anabnormalDGGEpatternidentifiedan R75Q mutation in the N1303K carrier and an L967S mutation in the G542X carrier.
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ABCC7 p.Asn1303Lys 11025834:53:344
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66 The patient having 2 CF mutations (No. 1624) had an elevated sweat chloride concentration (102 mmol/L) (normal level, Ͻ60 mmol/L).20 The N1303K carrier patient (No. 1344) had 2 borderline and 1 elevated sweat chloride concentration measurements (55, 58, and 78 mmol/L), while the re- Table 1.
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ABCC7 p.Asn1303Lys 11025834:66:143
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67 Cystic Fibrosis (CF) Mutations and Cystic Fibrosis Transmembrane Regulator (CFTR) Variants in Chronic Rhinosinusitis (CRS) Patients and Controls* CRS, No. (%) Non CRS, No. (%) P Value (n = 147) (n = 123) CF mutations ⌬F508/+ 1 2 ⌬F508/M470V 7 0 G542X/M470V, L967S 1 0 N1303K/+; M470V/M; R75Q/+† 1 0 (⌬F508/2789+5G→A)‡ 1 0 Frequency of CF carriers 10 (7) 2 (2) .04§ (n = 136) (n = 121) CFTR variants 5T Variant in non-CF carriers࿣ 5T/+ 11 (9) 6 (6) .25§ Codon 470 genotypes among non-CF carriers࿣ M/M 21 (16) 23 (19) M/V 55 (40) 64 (53) .03¶ V/V 60 (44) 34 (28) *Plus (+) indicates wildtype.
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ABCC7 p.Asn1303Lys 11025834:67:282
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84 Cystic Fibrosis Transmembrane Regulator (CFTR) Genotypes and Clinical Features of Chronic Rhinosinusitis Patients Having a Cystic Fibrosis Mutation* Patient No. Sex CFTR Genotype Age of Onset, y Sinus Surgery, No. of Times Polyposis Pulmonary Status Gastrointestinal Status Sweat Chloride Concentration, mmol/L† Other Pertinent Clinical Features 1344 F N1303K/+; M470V/M; R75Q/+‡ Ͻ10 3 - Recurrent bronchitis Lactose intolerant 55, 58, 78 .
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ABCC7 p.Asn1303Lys 11025834:84:360
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PMID: 11056144 [PubMed] Lewis-Jones DI et al: "Cystic fibrosis in infertility: screening before assisted reproduction: opinion."
No. Sentence Comment
85 Science, 245, 1073-1080.3659∆C 3849ϩ10KbC→T Lissens, W., Mercier, B., Tournaye, H. et al. (1996) Cystic fibrosis and infertility caused by congenital bilateral absence of the vas deferens andW1282X N1303K related clinical entities.
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ABCC7 p.Asn1303Lys 11056144:85:218
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PMID: 11076060 [PubMed] Tanackovic G et al: "The incidence of cystic fibrosis (CF) mutations among patients from Croatia."
No. Sentence Comment
5 After DNA isolation (2), we screened the samples for the 16 most common CFTR mutations: DF508, DI507 [heteroduplex analysis (3)] G542X, G551D, W1282X, N1303K, 3849+10kbC“T, R553X, 621+1G“T, R1162X, 1717-1G“A, 2789+ 5G“A, 3849+4A“G, 1898+1G“A, R117H [restriction fragment length polymorphism, (4-7)] and 3905insT [single-strand conformational polymorphism analysis (8)].
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ABCC7 p.Asn1303Lys 11076060:5:151
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7 The presence of six different mutations was observed on 60 CF chromosomes: DF508, G542X, 1717-1G“A, R117H, N1303K and R1162X (Table 1).
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ABCC7 p.Asn1303Lys 11076060:7:112
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17 The mutations N1303K, 1717-1G“A and R117H were represented with the same frequency of 3.3%.
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ABCC7 p.Asn1303Lys 11076060:17:14
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18 Mutation N1303K is relatively common in Italy (4.0%) and the Czech Republic (3.1%) (14, 16), with a lower frequency in Hungary (1.2%) and the Republic of Macedonia (1.8%), while in Slovenia, it appears with a frequency of 0.5% (personal communication) (13, 15).
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ABCC7 p.Asn1303Lys 11076060:18:9
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20 Results of CF mutation identification Location of the mutation in the CFTR geneMutation %CF chromosomes with mutation (n)* DF508 65.039exon 10 exon 11G542X 5.03 N1303K exon 21 2 3.3 1717-1G“A intron 10 2 3.3 2exon 4R117H 3.3 G85E 1.71exon 3 R1162X exon 19 1 1.7 Total identified - 50 83.3 *Sum of CF chromosomes from 30 patients is 60 (30×2).
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ABCC7 p.Asn1303Lys 11076060:20:161
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PMID: 11095651 [PubMed] Persu A et al: "CF gene and cystic fibrosis transmembrane conductance regulator expression in autosomal dominant polycystic kidney disease."
No. Sentence Comment
52 Genomic DNA samples were screened using the Elucigene CF12 kit (based on Amplification Refractory Mutation System technology; Zeneca Diagnostics, Abingdon, UK), to detect the following 12 CFTR mutations: 1717-1G3A, G542X, W1282X, N1303K, ⌬F508, 3849ϩ10kbC3T, 621ϩ1G3T, R553X, G551D, R117H, R1162X, and R334W.
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ABCC7 p.Asn1303Lys 11095651:52:230
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99 Characteristics of the 12 mutations of the CF gene screened for among the patients with ADPKD and the control subjectsa Name Location Nucleotide Change CFTR Domain Consequence R117H Exon 4 G3A at 482 TM2 Arg3His at 117 621ϩ1G3T Intron 4 G3T at 621ϩ1 mRNA splicing mutation R334W Exon 7 C3T at 1132 TM6 Arg3Trp at 334 ⌬F508 Exon 10 3-bp deletion between 1652 and 1655 NBD1 Phe-508 deletion 1717-1G3A Intron 10 G3A at 1717-1 NBD1 mRNA splicing mutation G542X Exon 11 G3T at 1756 NBD1 Gly3Stop at 542 G551D Exon 11 G3A at 1784 NBD1 Gly3Asp at 551 R553X Exon 11 C3T at 1789 NBD1 Arg3Stop at 553 R1162X Exon 19 C3T at 3616 Arg3Stop at 1162 3849ϩ10kbC3T Intron 19 C3T in a 6.2-kb EcoRI fragment 10 kb from 19 NBD2 Creation of a splice acceptor site W1282X Exon 20 G3A at 3978 NBD2 Trp3Stop at 1282 N1303K Exon 21 C3G at 4041 NBD2 Asn3Lys at 1303 a Modified from reference 16.
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ABCC7 p.Asn1303Lys 11095651:99:817
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PMID: 11100963 [PubMed] Choo-Kang LR et al: "Type I, II, III, IV, and V cystic fibrosis transmembrane conductance regulator defects and opportunities for therapy."
No. Sentence Comment
37 Molecular fate of CFTR protein Type of genetic defect and example Class-specific potential therapeutic approach Specific clinical examples I No synthesis Nonsense G542X Frameshift 394delTT Splice junction 1717-1G→A Aminoglycoside readthrough of premature termination site Gentamicin II Trafficking block AA deletion ∆F508 Missense N1303K Manipulation of intracellular folding environment (chemical or molecular chaperones) Phenylbutyrate, CPX III Block in regulation Missense G551D Stimulation of membrane localized mutant channel Genistein, MPB- compounds IV Altered conductance Missense R117H Augmentation of mutant channel conductance Milrinone, adenosine nucleotides V Reduced synthesis of normal protein Missense A455E Alternative splicing 3849+10kbC→T Maximal activation of decreased but functionally normal channels Stimulation of mRNA and protein synthesis ?
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ABCC7 p.Asn1303Lys 11100963:37:345
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PMID: 11117575 [PubMed] Kimura S et al: "Polymorphism of cystic fibrosis gene in Japanese patients with chronic pancreatitis."
No. Sentence Comment
128 Cohn et al (5) studied 27 patients with chronic idiopathic pancreatitis and detected three different mutations in eight patients: ⌬F508 in five, R117H in two, and N1303K in one.
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ABCC7 p.Asn1303Lys 11117575:128:170
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PMID: 11157821 [PubMed] McCallum T et al: "Unilateral renal agenesis associated with congenital bilateral absence of the vas deferens: phenotypic findings and genetic considerations."
No. Sentence Comment
61 ThereW1282X; ∆F508; R553X; N1303K; 3849ϩ10 kb C-T; R117L; I506; R553G; R560K; 1811ϩ1G-C; 1774delCT; S549R; S549I; R1283K; were no significant correlations with ethnic origin.
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ABCC7 p.Asn1303Lys 11157821:61:34
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PMID: 11158459 [PubMed] Wine JJ et al: "Comprehensive mutation screening in a cystic fibrosis center."
No. Sentence Comment
16 Mutations detected in both groups included 7 missense mutations (S13F, P67L, G98R, S492F, G970D, L1093P, N1303K) and 9 deletion, frameshift, nonsense or splicing mutations (R75X, G542X, ⌬F508, 451-458⌬8 bp, 5T, 663⌬T, exon 13 frameshift, 1261؉1G3A and 3272-26A3G).
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ABCC7 p.Asn1303Lys 11158459:16:105
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86 Mutations in the Stanford CF Mutation Database After Screening With the Genzyme70 Assay Mutation n % n % ⌬F508 353 67.11% 353 67.11% Splice mutations 16 3.04% 621ϩ1 G3T 5 0.95% 1717-1 G3A 5 0.95% 2789ϩ5 G3A 1 0.19% 1898ϩ1 G3A 1 0.19% 3849ϩ10 kb C3T 4 0.76% Stop mutations 31 5.89% Q493X 1 0.19% G542X 13 2.47% R553X 4 0.76% R1162X 1 0.19% W1282X 10 1.90% S1455X 2 0.38% Insertions/deletions 9 1.71% 681 del C 1 0.19% 2184 del A 2 0.38% 3859 del C 5 0.95% 3905 ins T 1 0.19% Missense mutations 33 6.27% G85E 4 0.76% R117H 3 0.57% R334W 6 1.14% G551D 14 2.66% R560T 3 0.57% N1303K 3 0.57% Unknown mutations 84 15.97% 84 15.97% Total 526 100.00% 526 100.00% ARTICLES tients with positive sweat tests were selected for SSCP/HA analysis based on clinical status, ethnicity, and previous screening with the Genzyme70 assay.
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ABCC7 p.Asn1303Lys 11158459:86:603
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115 Mutation Detection in 10 Participants With Positive Sweat Chloride Values I.D. Pancreatic Function Mutation Status Discovered Mutations (Novel) Polymorphisms SP1 PI N1303K/unk* L1093P (17b), M470V (10)* SP2 PI unk*/unk* S13F (exon1) 2184 ins A (exon 13) GATT7/7, 2694 T/G SP3 PS unk*/unk* ⌬451-458 (4); G970D (16) GATT7/6, 2694 T/G SP4 PS unk*/unk* R75X (3), G98R (4) GATT7/7, 492 G/A SP5 PS unk*/unk 3272-26A/G (17b) M470V/M470V (10) SP6 PI/PS (mild) ⌬F508/unk None found - SP7 PI ⌬F508/unk None found GATT6/7,1001ϩ11C/T (6b), M470V (10) SP8 PI unk*/unk S492F (10) GATT7/7 GT11/11 M470V/M470V SP9 PI ⌬F508/unk None found - SP10 PI unk*/unk* 663 ⌬T/663 ⌬T GATT6/6, 2694T3G Column labeled Pancreatic Function indicates the need for dietary supplementation with pancreatic enzymes.
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ABCC7 p.Asn1303Lys 11158459:115:165
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PMID: 11168023 [PubMed] Goldman A et al: "The molecular basis of cystic fibrosis in South Africa."
No. Sentence Comment
27 Five other mutations were identified in the white population, G542X, R553X, S549N, 621+lG“T and N1303K which together account for a further 3% of mutations (5).
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ABCC7 p.Asn1303Lys 11168023:27:101
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40 White and coloured patients with unidentified CF mutations were tested for 15 mutations including 394delTT, Q493X, 3272-26A“ G, 3120+1G“A as well as 11 other mutations, R117H, R334W, G542X, G551D, R553X, 621+ 1G“T, W1282X, N1303K, 1717-1G“A, R1162X, 3849+10kbC“T.
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ABCC7 p.Asn1303Lys 11168023:40:238
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PMID: 11243954 [PubMed] Marchand E et al: "Frequency of cystic fibrosis transmembrane conductance regulator gene mutations and 5T allele in patients with allergic bronchopulmonary aspergillosis."
No. Sentence Comment
6 All subjects in the study were screened for the presence of 13 mutations in the CFTR gene (R117H, 621 ؉ 1G->T, R334 W, ⌬F508, ⌬I507, 1717-1G->A, G542X, R553X, G551D, R1162X, 3849 ؉ 10kbC->T, W1282X, and N1303K).
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ABCC7 p.Asn1303Lys 11243954:6:229
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42 Genomic DNA samples were screened for the following CFTR mutations: R117H/ exon 4, 621 ϩ 1G-ϾT/intron 4, R334 W/exon 7, ⌬F508/exon 10, ⌬I507/exon 10, 1717-1G-ϾA/intron 10, G542X/exon 11, R553X/ exon 11, G551D/exon 11, R1162X/exon 19, 3849 ϩ 10kbC-ϾT/ intron 19, W1282X/exon 20, and N1303K/exon 21.
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ABCC7 p.Asn1303Lys 11243954:42:326
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PMID: 11298840 [PubMed] Attardo T et al: "Genetic, andrological and clinical characteristics of patients with congenital bilateral absence of the vas deferens."
No. Sentence Comment
49 We investigated the following 11 CFTR mutations: DF508, G542X, R553X, N1303K, W1282X, R347P, L1077P, 2183AA ® G, 1717±1G > A, R1162X, and R117H.
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ABCC7 p.Asn1303Lys 11298840:49:70
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PMID: 11313771 [PubMed] Henry MT et al: "An alpha1-antitrypsin enhancer polymorphism is a genetic modifier of pulmonary outcome in cystic fibrosis."
No. Sentence Comment
65 Non DF 508 alleles in the two groups were: 1237A group: G551D (3); N1303K (2); R117H (1); R560T (1); Unknown (3).
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ABCC7 p.Asn1303Lys 11313771:65:67
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66 1237G group: G551D (10); R117H (3); R560T (3); D1507 (2); E60X (2); N1303K (1); 1717-1 (1); 621H (1); G542X (1); POL 400 (1); R352Q (1); RT0F (1); 621+G4T (1); Unknown (15).
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ABCC7 p.Asn1303Lys 11313771:66:68
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70 For subjects heterozygous for DF508, the second allele was matched as closely as possible and included the following: G551D, N1303K, R117H and R560T.
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ABCC7 p.Asn1303Lys 11313771:70:125
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81 infective exacerbations over 2 years 4.7+0.7 2.8+0.6 0.03 over 4 yearsb 10.5+1.8 4.5+1.1 0.006 FEV1 % predicted 55.5+7.4 67.5+5.5 NS at reference visit 2 years post 53.1+8.5 68.4+5.5 (n=14) 0.09 (NS) reference visitb a Non DF 508 alleles in the two groups were: 1237A group: G551D (3); R117H (1); R560T (1); N1303K (2); Unknown (3); 1237G group: G551D (4); R117H (1); R560T (1); 621+G4T (1); Unknown (3).
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ABCC7 p.Asn1303Lys 11313771:81:308
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PMID: 11336401 [PubMed] Orgad S et al: "Prevalence of cystic fibrosis mutations in Israeli Jews."
No. Sentence Comment
33 These were: delF508 (Kerem et al., 1989), W1282X (Vidaud et al., 1990), G542X, 1717-1G R A, S549R (Kerem et al., 1990), N1303K (Osborn et al., 1991), 3849 1 10Kb C R T (Highsmith et al., 1994), T359K/Q360K (Shoshani et al., 1992), G85E (Zielenski et al., 1991), 405 1 1G R A (Dork et al., 1993), W1089X (Shosani et al., 1994), and D1152H (Highsmith et al., 1993).
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ABCC7 p.Asn1303Lys 11336401:33:120
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40 THE CONSENSUS POLICY OF SCREENING OF CF MUTATIONS IN ETHNIC GROUPS OF ISRAELI JEWSa Buchara and Iran Georgia Libya Morocco Tunis Turkey Egypt Sephardi W1089X 1 1 1 G85E 1 1 405-1 G® A 1 1 1 S549R 1 1 D1152H 1 1 1 1 T360K 1 Individuals of all ethnic groups were screened for the mutations W1282X, delF508, G5429X, N1303K, 3849110Kb C® T and 1717-1G® A.
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ABCC7 p.Asn1303Lys 11336401:40:318
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45 There were 173 (46.3%) carriers of the W1282X mutation; 110 (29.4%) carriers of delF508; 23 (6.1%) carriers of G542X; 10 (2.7%) carriers of N1303K; and 22 (5.9%) carriers of 3849 1 10KbC R T. Twenty (5.3%) were found to carry D1152H; 11 (2.9%) carried 405 1 1G R A; 4 (1.1%) carried W1089X; and 1 (0.3%) carried S549R. No carriers were detected for the mutations 1717-1G R A, G85E, and T360K, which were tested for in 7,383, 1,436, and 41 individuals, respectively.
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ABCC7 p.Asn1303Lys 11336401:45:140
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52 Mutations tested for all individuals in the cohort North Total Ashkenazi Sephardi Africa Eastern number of Mutation no. 6850 no. 933 no. 1146 no. 468 carriers W1282X 142 17 8 6 173 delF508 86 12.25 11.5 0.25 110 G542X 20.25 0.5 1.75 0.5 23 N1303K 7.5 1.5 0.25 0.75 10 3849110Kb 17 2 2 1 22 C® T B. Mutations tested for individuals of non-Ashkenazi origin, mixed origin, and of spouses of carriers Type of Total number mutation Number tested Ashkenazi Sephardi North Africa Eastern of carriers D1152H Number tested 1,305 458.25 722.75 280 Carriers 11.5 4.5 3.5 0.5 20 405 Number tested 425.75 372 633.5 119 11G® A Carriers 0.5 1 9.5 0 11 W1089X Number tested 539.25 345 638.5 135 Carriers 2 0.5 1 0.5 4 S549R Number tested 534.5 385.5 686 110 Carriers 0 1 0 0 1 a Ethnic origin was classified according to the country of origin of the four grandparents of each individual. Each grandparent was calculated as contributing a quarter of his/her gene pool and these were summed up for each ethnic origin.
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ABCC7 p.Asn1303Lys 11336401:52:240
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74 Therefore, Ashkenazi Jews would have been tested for the five main mutationsonly: delF508,W1282X, G542X, N1303K, and 3849 1 10KbC R T. The mutations D1152H and W1089X would not have been included in the test panel in Ashkenazi Jews.
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ABCC7 p.Asn1303Lys 11336401:74:105
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PMID: 11345141 [PubMed] Modolell I et al: "Gastrointestinal, liver, and pancreatic involvement in adult patients with cystic fibrosis."
No. Sentence Comment
50 In the remaining 14 patients, ⌬F508 was carried with G542X, R1162X, N1303K, L206W, 1717-1G>A, 711+1G>T, or an unidentified mutation.
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ABCC7 p.Asn1303Lys 11345141:50:75
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56 5T, G542X, R334W, N1303K, L206W, 3659-C, and G85E were identified in the remaining nine patients.
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ABCC7 p.Asn1303Lys 11345141:56:18
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64 Other genotypes present in our series ⌬F508/711+1G>T 2A 5T/5T 1B ⌬F508/5T 2B ⌬1507/- 1A ⌬F508/R117H 2B R1162X/1898+1G>A 1A ⌬F508/R1162X 1A 2183A/- 1A ⌬F508/N1303K 1A 1609-CA/1811+1.6kbA>G 1A ⌬F508/3272-26A>G 1B 1609-CA/R347P 1A ⌬F508/D836Y 1B Q890X/- 1A ⌬F508/1717-1G>A 1A R334W/- 1B G542X/W1282X 1A N1303K/2789+5G>A 1B G542X/2789+5G>A 1B 3659-C/- 1B G542X/P205S 1B G85E/- 1B G542X/D1270N 1B Negative 1A, 20B L206W/- 1B Unknown 2A creatic insufficiency was highly prevalent, affecting 33 patients (84.6%).
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ABCC7 p.Asn1303Lys 11345141:64:198
status: NEW
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ABCC7 p.Asn1303Lys 11345141:64:363
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PMID: 11388756 [PubMed] Heim RA et al: "Improved detection of cystic fibrosis mutations in the heterogeneous U.S. population using an expanded, pan-ethnic mutation panel."
No. Sentence Comment
109 More strikingly, the five mutations reported to account for 97% of Ashkenazi Jewish chromosomes (⌬F508, G542X, W1282X, N1303K, and 3849 ϩ 10 kbCϾT)16 accounted for only 39/48 chromosomes in this study (81.3%).
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ABCC7 p.Asn1303Lys 11388756:109:126
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PMID: 11404246 [PubMed] Choo-Kang LR et al: "Induction of HSP70 promotes DeltaF508 CFTR trafficking."
No. Sentence Comment
281 Whether this approach would also overcome the defects caused by other trafficking mutants such as N1303K, P574H, or G480C remains to be tested.
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ABCC7 p.Asn1303Lys 11404246:281:98
status: NEW
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PMID: 11404347 [PubMed] Slatkin M et al: "The use of intraallelic variability for testing neutrality and estimating population growth rate."
No. Sentence Comment
253 the recent growth rate of European populations is not TABLE 2 Parameters and results for the CFTR data sets p n N0 ␮ ϭ 0.0001 ␮ ϭ 0.0005 ␮ ϭ 0.001 ␮ ϭ 0.0005 Mutation (ϫ10-4 ) i So (ϫ103 ) (ϫ107 ) (single) (single) (double) (double) ⌬F508 132 2112 59 160.0 20.0 0.0 0.0 6.0 ϫ 10-73 6.3 ϫ 10-21 ⌬F508 132 2112 118 160.0 20.0 0.0 5.5 ϫ 10-91 4.4 ϫ 10-39 1.0 ϫ 10-4 G542X 6.8 116 9 170.6 5.82 8.9 ϫ 10-8 0.012 0.231 0.907 N1303K 5.6 59 7 105.3 5.18 5.9 ϫ 10-4 0.180 0.639 0.977 1717-1G-A 3.2 24 3 75.0 4.38 0.031 0.370 0.695 0.945 R1162X 2.2 68 4 309.1 5.18 3.4 ϫ 10-4 0.082 0.313 0.829 Definitions are as in Table 1, except the mutation rates.
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ABCC7 p.Asn1303Lys 11404347:253:541
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271 TABLE 3 Values of ␹2 ϭ -2 log(L0/L*) calculated as described in the text for each allele at CFTR compared to the rest ␮ ϭ 0.00028: ␮ ϭ 0.00028: ␮ ϭ 0.00084: ␮ ϭ 0.00084: Mutation So ϭ 59 So ϭ 118 So ϭ 59 So ϭ 118 ⌬F508 20.3 11.0 19.6 4.6 G542X 5.8 1.4 5.4 0.8 N1303K 8.4 3.8 7.9 3.0 1717-1G-A 3.4 0.5 3.5 1.0 R1162X 1.8 0.6 1.6 0 So was estimated by using a parsimony algorithm to infer because they depend on assumed values of parameters and on a simplified model of past population growth.the minimum number of mutations necessary to gener- The results for CFTR are compatible with those for PAHate the observed haplotypes.
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ABCC7 p.Asn1303Lys 11404347:271:356
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PMID: 11462247 [PubMed] Castellani C et al: "Analysis of the entire coding region of the cystic fibrosis transmembrane regulator gene in idiopathic pancreatitis."
No. Sentence Comment
41 Genetic analysis Phase 1 - Patients were tested for the following mutations: F508del, I507del, R117H, R1162X, 2183AA>G, N1303K, 3849+10KbC>T, G542X, 1717-1G>A, R347P, R352Q, R553X, Q552X, G85E, 711+5G>A, W1282X, 3132delTG and 2789+5G>A, plus the CFTR intron 8 poly(T) tract length.
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ABCC7 p.Asn1303Lys 11462247:41:120
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63 PATIENT A B C Sex (m/f) f f f Age (yrs) 27 60 53 Pancreatitis ICP IRAP IRAP CFTR mutations R1162X 2789+5G→A N1303K R117H R553X PolyT Splice Variant 7/7 7/9 7/9 Sweat Cl- (mEq/l) 108 42 91.75 Sweat Na+ (mEq/l) 106.5 42.8 84.25 NPD n.a. Basal and activated positive Basal negative, activated positive CF-compatible anamnestical and clinical features Chronic cough Lobectomy for bronchiectasis; hemoptysis and bronchial artery embolization Lobar atelectasis Sputum culture Staphylococcus aureus; Pseudomonas aeruginosa Staphylococcus aureus Staphylococcus aureus; Pseudomonas aeruginosa FVC (% predicted) 94 107 118 FEV1 (% predicted) 79 93 116 FEF25-75 (% predicted) 45 49 127 Chest X-ray Chrispin-Norman score 4 3 5 X-ray mucosal thickening of paranasal sinuses Maxillary bilateral Frontal bilateral Maxillary right Weight Z-score -0.86 0.08 -0.53 Height Z-score -0.28 -0.45 -0.12 Pancreatic evaluation § * Pancreatic sufficiency Pancreatic sufficiency n.a. : not available § : duodenal outputs of bicarbonate, lipase, amylase, trypsin and chymotrypsin assessed by pancreatic stimulation test * : normal fecal chymotrypsin and 72-hour steatorrhea The medical history disclosed in 20/53 (37.7%) cases one or more signs and symptoms frequently found in CF: diabetes in 9, sinusitis in 8, chronic cough in 7, malnutrition in 1, monolateral seminal vesicle agenesis in 1, lobectomy secondary to bronchiectasis in 1 and lobar atelectasis in 1 subject.
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ABCC7 p.Asn1303Lys 11462247:63:115
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81 She is a compound heterozygote, carrying N1303K and R117H.
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ABCC7 p.Asn1303Lys 11462247:81:41
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PMID: 11484207 [PubMed] Orozco L et al: "XV-2c/KM-19 haplotype analysis of cystic fibrosis mutations in Mexican patients."
No. Sentence Comment
46 Among those found in more than one chromosome, S549N was associated only with haplotype A, N1303K only with haplotype B, DI507 only with D, and 2055del9!A only with A.
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ABCC7 p.Asn1303Lys 11484207:46:91
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54 This ®gure is much lower than in European populations (48.8%) where several mutations such as G551D, N1303K, and W1282X are relatively frequent and associated with haplotype B (EWGCFG, 1990; Castaldo et al., 1996].
X
ABCC7 p.Asn1303Lys 11484207:54:106
status: NEW
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65 Distribution of XK Haplotype on Chromosomes Bearing Uncommon Cystic Fibrosis (CF) Mutations A B C D S549N 4/4 DI507 3/3 N1303K 3/3 2055 del9!A 2/2 I148T 1/1 406-1G!A 1/1 R75X 1/1 I506T 1/1 935delA 1/1 2183AA!G 1/1 1924del7 1/1 G551S 1/1 1078delT 1/1 R117H 1/1 3849‡10KbC!T 1/1 1716G!A 1/1 W1204X 1/1 W1098C 1/1 846delT 1/1 R75Q 1/1 W1069X 1/1 L558S 1/1 4160insGGGG 1/1 297-1G!A 1/1 Fig.
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ABCC7 p.Asn1303Lys 11484207:65:120
status: NEW
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88 In contrast, we identi®ed one 3849‡10kbC!T chromosome associated with haplotype C, as previously reported in Israel [Sereth et al., 1993], but differing from the Pueblo Amerindians, where this mutation was associated with haplotype A; the 2183AA!G chromosome was associated with haplotype D, but had been previously found on a B haplotype in Italy; N1303K was found on three haplotype B chromosomes, whereas in southern Europe this mutation has been associated mainly with haplotype B, but also with haplotypes A, C, and D [Petreska et al., 1998; Castaldo et al., 1996; Borrego et al., 1994; Claustres et al., 1996].
X
ABCC7 p.Asn1303Lys 11484207:88:359
status: NEW
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PMID: 11491164 [PubMed] Massie RJ et al: "Intron-8 polythymidine sequence in Australasian individuals with CF mutations R117H and R117C."
No. Sentence Comment
41 Infants with a positive (w60 mmol?L-1 ) or borderline (40 - 60 mmol?L-1 ) sweat chloride and in whom there is an unidentified mutation are referred for an extended mutation analysis which includes: DF508, R117H, G551D, A455E, G542X, N1303K, W1282X, 1717-1, R560T, R347P, R334W, R1162X, S549N, 621z1, 3849z10CwT, and the IVS8 polythymidine sequence.
X
ABCC7 p.Asn1303Lys 11491164:41:233
status: NEW
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PMID: 11504857 [PubMed] Chen JM et al: "A combined analysis of the cystic fibrosis transmembrane conductance regulator: implications for structure and disease models."
No. Sentence Comment
100 Moreover, all of the 11 most common missense mutations or single-amino-acid deletions (i.e., F508del, G551D, N1303K, R117H, R347P, I507del, G85E, R560T, A455E, R334W, and S549N) identified in classic and atypical CF patients worldwide (http://www.genet.sickkids.on.ca/cftr) occur in stringently conserved residues across the 15 CFTR sequences.
X
ABCC7 p.Asn1303Lys 11504857:100:109
status: NEW
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PMID: 11523757 [PubMed] Dawson KP et al: "The S549R (T-->G) cystic fibrosis gene mutation."
No. Sentence Comment
29 Sporadic examples of other mutations occur, such as homozygous examples of N1303K.
X
ABCC7 p.Asn1303Lys 11523757:29:75
status: NEW
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PMID: 11568116 [PubMed] Jenison R et al: "Silicon-based biosensors for rapid detection of protein or nucleic acid targets."
No. Sentence Comment
68 Capture sequences were as follows: For ⌬F508, the wild type was 5Ј-YAC AAC ACC AAA GAT GAT ATT TT-3Ј, and the mutant was 5Ј-YCC GAA ACA CCA ATG ATA TTT TC-3Ј For N1303K, the wild type was 5Ј-YAC GGA TCC AAG TTT TTT CTA A-3Ј, and the mutant was 5Ј-YAC GGA TCC AAC TTT TTT CTA A-3Ј For G551D, the wild type was 5Ј-YAA CTC GTT GAC CTC CAC TC-3Ј, and the mutant was 5Ј-YAA CTC GTT GAT CTC CAC TC-3Ј For G542X, the wild type was 5Ј-YAA CAC CTT CTC CAA GAA CTA TA-3Ј, and the mutant was 5Ј-XAA CAC CTT CTC AAA GAA CTA TA-3Ј antibody immobilization Capture antibodies were diluted to 2 mg/L in 0.1 mol/L sodium bicarbonate buffer, pH 9.3, and 200 nL was spotted using a Hamilton MP2200 pipetting robot equipped with a modified dispense head.
X
ABCC7 p.Asn1303Lys 11568116:68:193
status: NEW
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79 Input concentrations for the probe sets was as follows: ⌬F508, 150 nmol/L for both the wild type and mutant; G542X, 75 nmol/L for the wild type and 750 nmol/L for the mutant; N1303K, 300 nmol/L for both the wild type and mutant; G551D, 150 nmol/L for both the wild type and mutant.
X
ABCC7 p.Asn1303Lys 11568116:79:182
status: NEW
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119 One mutation, ⌬F508, is a 3-bp deletion, whereas the other three, G542X, G551D, and N1303K, are SNPs.
X
ABCC7 p.Asn1303Lys 11568116:119:91
status: NEW
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PMID: 11569691 [PubMed] Truninger K et al: "Mutations of the cystic fibrosis gene in patients with chronic pancreatitis."
No. Sentence Comment
56 Using multiplex PCR, 15 genomic fragments were amplified which contain the following mutations: ⌬F508, ⌬I507, Q493X, V520F, 1717-1G3A, G542X, G551D, R553X, R560T, S549R, S549N, 3849 ϩ 10kbC3T, 3849 ϩ 4A3G, R1162X, 3659delC, W1282X, 3905insT, N1303K, G85E, 621 ϩ 1G3T, R117H, Y122X, 711 ϩ 1G3T; 1078delT, R347P, R347H, R334W, A455E, 1898 ϩ 1G3A, 2183AA3G, 2789 ϩ 5G3A.
X
ABCC7 p.Asn1303Lys 11569691:56:268
status: NEW
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PMID: 11574497 [PubMed] Josserand RN et al: "Cystic fibrosis phenotype evaluation and paternity outcome in 50 males with congenital bilateral absence of vas deferens."
No. Sentence Comment
30 Leukocytes samples were analysed for a series of 22 CF mutations including the five most frequently encountered in our region (The CF Genotype Consortium, 1994): ∆F508, G542X, N1303K, 1717-G-A, 885E; and 17 others: R117H, R334W, R347H, R347P, 556delA, S549N, S549I, S549R, G551D, R553X, R560T, G1244E, S1255X, W1282X, R1283K, 3898ins C, D1270N.
X
ABCC7 p.Asn1303Lys 11574497:30:183
status: NEW
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PMID: 11589722 [PubMed] Walkowiak J et al: "Analysis of exocrine pancreatic function in cystic fibrosis: one mild CFTR mutation does not exclude pancreatic insufficiency."
No. Sentence Comment
5 Results Severe pancreatic insufficiency was associated with the presence of two CFTR gene mutations (DF508, N1303K, CFTR dele 2,3 (21kb), G542X, 1717±1G-A, R533X, W1282X, 621GT, 2183AAG, R560T, 2184insA and DI507, G551D, 895T) and mild insufficiency with the presence of at least one mutation (R117H, 3171insC, A155P2, 138insL, 296 1 1G-A, E92GK, E217G, 2789 1 5G-A.
X
ABCC7 p.Asn1303Lys 11589722:5:108
status: NEW
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51 Results Among 394 genotyped CF patients, the following mutations on alleles were found (n): DF508 (464), 3849 1 10kbC-T (30), CFTR dele2,3(21 kB) (21), N1303K (15), G542X (12), 1717±1G-A (9), R533X (6), W1282X (6), 621 1 G-T (3), R117H (2), 3171insC (2), A155P2 (2), 2183AAG (2), R334W (2), 895T (2), 296 1 1G-A (2), E92GK (2), 138insL (1), E217G (1), 2789 1 5G-A (1), R347P (1), R560T (1), 2184insA (1), I507 (1), G551D (1).
X
ABCC7 p.Asn1303Lys 11589722:51:152
status: NEW
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57 CFTR gene mutations were classified as `severe' (E1 , 96 mg g21 ) ± severely affecting pancreatic function (DF508, N1303K, CFTR dele 2,3 (21kb), G542X, 1717±1G-A, R533X, W1282X, 621 1 1G-T, 2183AAG, 895T, R560T, 2184insA, DI507, G551D) and `mild' (E1 .
X
ABCC7 p.Asn1303Lys 11589722:57:120
status: NEW
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81 500 DF508/3849 1 10kbC-T (17) 1 4 1 6 5 DF508/CFTR dele2,3(21kb) (15) 9 4 2 DF508/N1303K (10) 7 3 DF508/1717±1G-A (7) 5 2 DF508/G542X (7) 4 2 1 DF508/W1282X (5) 4 1 DF508/R553X (3) 3 DF508/R334W (2) 1 1 DF508/2183AAG (2) 2 DF508/R117H (1) 1 DF508/621GT (1) 1 DF508/R347P (1) 1 DF508/2184insA (1) 1 DF508/DI507 (1) 1 3849 1 10kbC-T/3849 1 10kbC-T (3) 3 N1303K/CFTR dele2,3(21kb) (2) 1 1 1717±1G-A/3849 1 10kbC-T (2) 1 1 3171insC/A155P2 (2) 1 1 296 1 1G-A/E92GK (2) 2 R117H/138insL (1) 1 W1282X/3849 1 10kbC-T (1) 1 N1303K/3849 1 10kbC-T (1) 1 CFTR dele2,3(21kb)/3849 1 10kbC-T (1) 1 R553X/G542X (1) 1 621 1 1G-T/621 1 1G-T (1) 1 G542X/M (4) 2 2 CFTR dele 2,3(21kb)/M (1) 1 2 3849 1 10kbC-T/M (2) 1 1 R533X/M (2) 2 N1303K/M (2) 2 895T/M (2) 1 1 E217G/M (1) 1 G551D/M (1) 1 R560T/M (1) 1 2789 1 5G-A/M (1) 1 Total (109) 44 21 10 4 12 18 M, unidentified mutation.
X
ABCC7 p.Asn1303Lys 11589722:81:82
status: NEW
X
ABCC7 p.Asn1303Lys 11589722:81:357
status: NEW
X
ABCC7 p.Asn1303Lys 11589722:81:524
status: NEW
X
ABCC7 p.Asn1303Lys 11589722:81:723
status: NEW
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88 An international Cystic Fibrosis Genotype-Phenotype Consortium [25] evaluated DF508 homozygotes and seven of the most common DF508 compound heterozygotes (G542X, R553X, N1303K, W1282X, 1717±1G-A, 621 1 1GT, R117H).
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ABCC7 p.Asn1303Lys 11589722:88:169
status: NEW
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90 N1303K was found to be a severe mutation in addition to E827X, W846X, while 4382delA, 3272±26G-A and 3849 1 10kbCT were assessed as mild ones [8].
X
ABCC7 p.Asn1303Lys 11589722:90:0
status: NEW
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PMID: 11668613 [PubMed] Wong LJ et al: "Improved detection of CFTR mutations in Southern California Hispanic CF patients."
No. Sentence Comment
117 Summary of Mutations Found in This Group of Hispanic Patients Exon or Number of Mutation intron chromosomes Frequency % Mutations detected before full gene analysis 91 73.38% 1 F508 10 64 51.6 2 G542X 11 5 4 3 3849+10kb C>T Intron 19 5 4 4 S549N 11 3 2.4 5 I148T 4 2 1.6 6 3120+1G>A 16 2 1.6 7 R334W 7 2 1.6 8 G551D 11 1 0.8 9 N1303K 21 1 0.8 10 W1282X 20 1 0.8 11 R1162X 19 1 0.8 12 G85E 3 1 0.8 13 W1089X 17b 1 0.8 14 Y1092X 17b 1 0.8 15 P205S 6a 1 0.8 Mutations detected by full gene screening 26 20.97% 16 R1066Ca 17b 2 1.6 17 1949del84 13 1 0.8 18 2184delA 13 1 0.8 19 Q98R 4 1 0.8 20 R75X 3 1 0.8 21 G1244E 20 1 0.8 22 3876delA 20 7 5.65 23 935delA 6b 2 1.6 24 406-1G>A Intron 2 2 1.6 25 3271delGG 17a 1 0.8 26 2105-2117del13insAGAAA 13 1 0.8 27 663delT 5 1 0.8 28 3171delC 17a 1 0.8 29 2108delA 13 1 0.8 30 Q179K 5 1 0.8 31 3199del6 17a 1 0.8 32 3500-2 A->T Intron 17b 1 0.8 Total identified 117 (177)b 94.35 (97.5)b Unidentified 7 (3)b 5.65 (2.5)b Total 124 (120)b 100 (100)b a This mutation was also detected by SSCP.
X
ABCC7 p.Asn1303Lys 11668613:117:327
status: NEW
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PMID: 11756355 [PubMed] Dohle GR et al: "Genetic risk factors in infertile men with severe oligozoospermia and azoospermia."
No. Sentence Comment
29 Twelve common mutations of the CFTR gene were tested (∆F508, A445E, G542X, 1717-1G→A, R553X, R117H, R1162X, N1303K, W1282X, 3659delC, E60X and S1251N).
X
ABCC7 p.Asn1303Lys 11756355:29:122
status: NEW
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PMID: 11781704 [PubMed] Larriba S et al: "ATB(0)/SLC1A5 gene. Fine localisation and exclusion of association with the intestinal phenotype of cystic fibrosis."
No. Sentence Comment
151 Statistical analysis showed that the higher incidence for P17A and the lower incidence for V512L observed in the general population Table 3 CFTR mutations of the CF patients under study with and without meconium ileus (MI) CF-non MI CF-MI CFTR mutations n CFTR mutations n F508del/R117H 2 F508del/F508del 7 F508del/R334W 3 F508del/L365P 1 F508del/R347P 1 F508del/G542X 1 F508del/621+1G4Ta 1 F508del/621+IG4Ta 1 F508del/M1101K 1 F508del/R1066C 1 F508del/1609delCAa 1 F508del/W1089X 1 F508del/2789+5G4Aa 3 F508del/R1162X 1 F508del/3849+10kbC4T 1 F508del/1609delCAa 1 G542X/G85E 1 F508del/Q1281X 1 G542X/V232D 1 F508del/1811+1.6kbA4G 1 G542X/1811+1.6kb A4Ga 1 F508del/2789+5G4Aa 1 G542X/2789+5G4A 1 F508del/2869insG 1 Q890X/L206W 1 F508del/unknown 1 1811+1.6kbA4G/P205S 1 I507del/I507del 1 R1162X/3272-26A4G 1 G542X/1078delT 1 N1303K/R347H 1 G542X/1811+1.6kbA4Ga 1 N1303K/A1006E+5T 1 S549R/CFTR50kbdel 1 2789+5G4A/405+1G4A 1 R1066C/R1066C 1 W1282X/712-1G4T 1 a CF patient with a sibling presenting identical CFTR genotype and discordance of intestinal phenotype.
X
ABCC7 p.Asn1303Lys 11781704:151:824
status: NEW
X
ABCC7 p.Asn1303Lys 11781704:151:862
status: NEW
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PMID: 11788089 [PubMed] Bombieri C et al: "Cystic fibrosis mutation testing in Italy."
No. Sentence Comment
35 CF MUTATIONS IDENTIFIED IN TWO ITALIAN REGIONS (VENETO AND TRENTINO ALTO ADIGE) Number of alleles Frequency Cumulative Mutation with mutation (%) frequency (%) DF508 107 47.6 47.56 R1162X 22 9.8 57.33 2183 AA ® G 21 9.3 66.67 N1303K 9 4.0 70.67 G542X 6 2.7 73.33 711 1 5 G ® A 6 2.7 76.00 1717-1 G ® A 5 2.2 78.22 G85E 3 1.3 79.56 R553X 3 1.3 80.89 2789 1 5 G ® A 3 1.3 82.22 Q552X 3 1.3 83.56 621 1 1 G ® T 2 0.9 84.44 W1282X 2 0.9 85.33 R347P 1 0.4 85.77 G551D 1 0.4 86.21 3849 1 10 Kb C ® T 1 0.4 86.67a 3132 del TG 2 0.9 87.54 2790-2 A ® G 2 0.9 88.43 457 TAT ® G 1 0.4 88.87 1717-8 G ® A 1 0.4 89.31 R709X 1 0.4 89.75 1898 1 3 A ® G 1 0.4 90.22 Total 203 90.22 Numbers refer to CFTR gene alleles carrying the specified mutation, over total tested alleles (n 5 225) from the affected subjects CF cohort, as indicated in the text (from Bonizzato et al., 1995).
X
ABCC7 p.Asn1303Lys 11788089:35:231
status: NEW
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38 CF MUTATION PANEL (VENETO AND TRENTINO ALTO ADIGE ITALIAN REGIONS) DF508 R1162X 2183 AA ® G N1303K G542X 711 1 5 G ® A 1717-1 G ® A G85E R553X 2789 1 5 G ® A Q552X 621 1 1 G ® T W1282X R347P G551D 3849 1 10 Kb C ® T Note: Contrary to what is suggested for the U.S. population (Grody et al., 2001), R117H mutation (and its reflex IVS8-5T test) is not included in the panel because it is not commonly found in the Italian CF population (Bonizzato et al., 1995; Estivill et al., 1997; Rendine et al., 1997).
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ABCC7 p.Asn1303Lys 11788089:38:97
status: NEW
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44 CF GENE MUTATIONS IN ITALY Number of alleles Frequency Cumulative Mutation screened (%) frequency (%) DF508 3442 51.07 51.07 N1303K 3056 4.84 55.91 G542X 3082 4.83 60.75 2183 AA ® G 2596 2.66 63.41 R1162X 2580 2.42 65.83 1717-1 G ® A 2892 2.11 67.94 W1282X 2600 1.23 69.17 R553X 2882 1.15 70.31 T338I 2306 0.69 71.01 R347P 2642 0.61 71.61 711 1 5 G ® A 2454 0.57 72.18 G85E 1980 0.40 72.59 621 1 1 G ® T 2594 0.39 72.97 R334W 2366 0.30 73.27 R352Q 2112 0.24 73.50 S549N 2118 0.24 73.74 R347H 2184 0.18 73.92 L1077P 1840 0.16 74.09 R1158X 1878 0.16 74.25 541del C 1884 0.16 74.40 R1066H 1918 0.16 74.56 E585X 1922 0.16 74.72 Q552X 2172 0.14 74.86 D1152H 1824 0.11 74.97 2790-2 A ® G 1862 0.11 75.07 3132 del TG 1862 0.11 75.18 3667ins 4 1876 0.11 75.29 DI507 1914 0.10 75.39 1898 1 3 A ® G 1920 0.10 75.50 G1244E 1960 0.10 75.60 1784 del G 2052 0.10 75.69 From Rendine et al. (1997).
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ABCC7 p.Asn1303Lys 11788089:44:125
status: NEW
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PMID: 11788611 [PubMed] Berger AL et al: "Mutations that change the position of the putative gamma-phosphate linker in the nucleotide binding domains of CFTR alter channel gating."
No. Sentence Comment
160 The single-channel gating of CFTR-N1303K, a relatively frequent CF-associated mutation, showed a long burst duration and a long interburst interval (Fig. 8).
X
ABCC7 p.Asn1303Lys 11788611:160:34
status: NEW
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168 between CFTR-N1303K and CFTR-K1250A, we examined the effect of PPi and ADP.
X
ABCC7 p.Asn1303Lys 11788611:168:13
status: NEW
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169 The N1303K mutation prevented PPi-dependent stimulation of current and eliminated ADP-dependent current inhibition (Fig. 9).
X
ABCC7 p.Asn1303Lys 11788611:169:4
status: NEW
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170 Pyrophosphate caused only a 26.9 Ϯ 18.6% (n ϭ 4) increase in current for the CFTR-N1303K channel, and ADP caused only a 3.2 Ϯ 6.8% (n ϭ 3) inhibition in current.
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ABCC7 p.Asn1303Lys 11788611:170:94
status: NEW
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180 Comparison of single-channel kinetics of CFTR-N1303K, CFTR-N1303H, CFTR-N1303I, and CFTR-N1303A.
X
ABCC7 p.Asn1303Lys 11788611:180:46
status: NEW
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184 Pyrophosphate and ADP did not affect CFTR-N1303K.
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ABCC7 p.Asn1303Lys 11788611:184:42
status: NEW
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187 Addition of 4 mM PPi increased the burst duration of wild type CFTR but did not alter the burst duration of CFTR-N1303K. The addition of 1 mM ADP increased the interburst interval of CFTR but did not affect CFTR-N1303K. with mutation of the NBD1 Walker A lysine (9, 10, 22, 35).
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ABCC7 p.Asn1303Lys 11788611:187:113
status: NEW
X
ABCC7 p.Asn1303Lys 11788611:187:212
status: NEW
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207 N1303K is a frequent CF-associated mutation that has been shown to affect channel processing (42).
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ABCC7 p.Asn1303Lys 11788611:207:0
status: NEW
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PMID: 11796434 [PubMed] Loubieres Y et al: "Association between genetically determined pancreatic status and lung disease in adult cystic fibrosis patients."
No. Sentence Comment
31 The most frequent CF mutations usually found in the French population (⌬F508, ⌬I507, 1717-1G3A, G542X, G551D, R553X, W1282X, N1303K) were analyzed by polymerase chain reaction and allele-specific oligonucleotide with the INNO-LIPA CF2 kit (Innogenetics; Zwijnaarde, Belgium).
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ABCC7 p.Asn1303Lys 11796434:31:139
status: NEW
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PMID: 11804840 [PubMed] Mall M et al: "Activation of ion secretion via proteinase-activated receptor-2 in human colon."
No. Sentence Comment
50 Testing of an additional panel of the 19 most prevalent CFTR mutations among the Caucasian population in Europe, including G542X, N1303K, 1717-1 GϾT, W1282X, G551D, R553X, R1162X, R334W, R117H, 621ϩ1GϾT, 3849ϩ10kbCϾT, 3659delC, 1078delT, R347P, A445E, S1251N, ⌬I507, 2183AAϾG, and E60X (ELUCIGENE CF20; AstraZeneca Diagnostics) failed to identify the second disease causing mutation in six CF patients.
X
ABCC7 p.Asn1303Lys 11804840:50:130
status: NEW
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PMID: 11824793 [PubMed] Teich N et al: "Genetic risk factors in chronic pancreatitis."
No. Sentence Comment
70 Approximately 72% of patients with cystic fibrosis are homozygous or compound heterozygous for eight mutations of the CFTR gene on chromosome 7: delta F508, G542X, R553X, W1282X, N1303K, 621 ϩ 1GÆT, 1717-1GÆA, and R117H; whereas the deletion delta F508 alone accounts for about 66% of mutant cystic fibrosis alleles.
X
ABCC7 p.Asn1303Lys 11824793:70:179
status: NEW
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PMID: 11866018 [PubMed] Spitzer E et al: "Identification of a new cystic fibrosis transmembrane regulator mutation in a severely affected patient."
No. Sentence Comment
31 Discussion Studies carried out in southern European populations, including the former Yugoslavia, identified DF508, G542X, G551D, 621z1GwT, W1282X and N1303K as the most common CF mutations [6, 7].
X
ABCC7 p.Asn1303Lys 11866018:31:151
status: NEW
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PMID: 11883825 [PubMed] Padoan R et al: "Genetic and clinical features of false-negative infants in a neonatal screening programme for cystic fibrosis."
No. Sentence Comment
8 The cystic brosis transmembrane regulator (CFTR) gene mutations identi ed were delF508, D1152H, R1066C, R334W, G542X, N1303K, F1052V, A120T, 3849 ‡ 10kbC ® T, 2789 ‡ 5G ® A, 5T-12TG and the novel mutation D110E.
X
ABCC7 p.Asn1303Lys 11883825:8:118
status: NEW
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34 It was initially performed by polyacrylamide gel electrophoretic (PAGE) analysis for the delF508 mutation, and later by polymerase chain reaction (PCR) and oligonucleotide ligation assay (OLA) (31 mutations: G85E, 621 ‡ 1G ® T, R117H, Y122X, 711 ‡ 1G ® T, 1078delT, R347P, R347H, R334W, A455E, 1898 ‡ 1G ® A, 2183-AA ® G, 2789 ‡ 5G ® A, DelF508, I507del, Q493X, V520F, 1717-1G ® A, G542X, G551D, R553X, R560T, S549R, S549N, 3849 ‡ 10kbC ® T, 3849 ‡ 4A ® G, R1162X, 3659delC, W1282X, 3905insT, N1303K) (14).
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ABCC7 p.Asn1303Lys 11883825:34:575
status: NEW
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40 Mutation Frequency (%) DelF508 54 N1303K 8 G542X 6.25 1717-1G ® A 2.50 R334W 1.75 2183AA ® G 1.50 R117H, L1077P, W1282X 1.25 D110E, R347P, E585X, 2789 ‡ 5G ® A 0.75 R352Q, R553X, R1066H, D1152H, R1158X, 1782delA, 1898 ‡ 1G ® A, 3659delC 0.50 G85E, R117L, G178R, D579G, H609R, Y1032C, V1153E, R1162X, 621 ‡ 1G ® T, 711 ‡ 1G ® T, 1845delAG o 1846delGA, 2143delT 0.25 Table2.Differencesinthethreestrategiesofneonatalscreening(audit1990-1999).
X
ABCC7 p.Asn1303Lys 11883825:40:34
status: NEW
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70 Year of birth Patient Sex Age at diagnosis Genotype Sweat test (chloride mEq l¡1 ) 1990 1 BA F 8 mo DF508/2789 ‡ 5G ® A 74, 79 2 LG M 4 y ¡/¡ 84, 83 1991 3 BV F 6 y ¡/¡ a 61, 85, 70 4 CA F 8 y R1066C/D1152H 58, 59 5 CA F 8 y DF508/5T-TG12 65, 67 6 PS M 5 y N1303K/-a 41, 43, 55, 63, 85, 89 1992 7 AE F 1 y R334W/-a 57, 42, 78, 82 8 DA M 4 mo ¡/¡ 85, 101, 143, 9 FA M 1 y ¡/¡ a 70, 75, 98, 114 1993 10 CA F 7 y DF508/5T-TG12 45, 50 1995 11 BM M 3 y DF508/DF508 117, 123 1997 12 DG M 6 mo G542X/D110E 59, 88, 80, 70 13 DE F 2 y D1152H/3849 ‡ 10kbC ® T 31, 35 14 TL M 2 y ¡/¡ a 115, 136 1998 15 CM M 5 mo F1052V/A120T 20, 25 F: female; M: male.
X
ABCC7 p.Asn1303Lys 11883825:70:294
status: NEW
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80 The CFTR alterations identi ed were D1152H, R1066C, R334W, G542X, N1303K, F1052V, A120T, 3849 ‡ 10kbC ® T, 2789 ‡ 5G ® A, 5T-12TG and the new mutation D110E (19).
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ABCC7 p.Asn1303Lys 11883825:80:66
status: NEW
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PMID: 11897641 [PubMed] Selvadurai HC et al: "The relationship between genotype and exercise tolerance in children with cystic fibrosis."
No. Sentence Comment
15 The most common mutation, ⌬F508 and the N1303K mutation belong to class II mutations and result in defects in protein processing.
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ABCC7 p.Asn1303Lys 11897641:15:47
status: NEW
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82 II ⌬F508 (36), W1282X (1) III G551D (10), N1303K (4), R560T (2), A559T (1) IV R117H (14), R347H (3) V 3849 ϩ 10KbC→T (7), 3120G→A (3) AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 165 2002 All patients were recruited from a single center, and the sample size of this study was large compared with previously published studies of exercise capacity in children with CF (21).
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ABCC7 p.Asn1303Lys 11897641:82:49
status: NEW
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PMID: 11929516 [PubMed] Theiss S et al: "Functional analysis of a vacuolar ABC transporter in wild-type Candida albicans reveals its involvement in virulence."
No. Sentence Comment
72 Interestingly, a DF508 deletion or a N1303K mutation in CFTR is a cause for human cystic fibrosis.
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ABCC7 p.Asn1303Lys 11929516:72:37
status: NEW
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84 Deletion of F508 or a N1303K mutation in CFTR causes human cystic fibrosis.
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ABCC7 p.Asn1303Lys 11929516:84:22
status: NEW
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PMID: 11933191 [PubMed] Ravnik-Glavac M et al: "DHPLC screening of cystic fibrosis gene mutations."
No. Sentence Comment
42 The following mutations have been studied: exon 3: W57G, R74W, R75Q, G85E, 394delTT, 405+ 1G>A; exon 4: E92X, P99L, 441delA, 444delA, 457TAT>G, D110H, R117C, R117H, A120T, 541delC, 544delCA, Q151X, 621+1G>T, 662- 2A>C; exon 7: 1078delT, F331L, R334W, I336K, R347C, R347P, A349V, R352Q, 1221delCT; exon 10: S492F, Q493X, 1609delCA, deltaI507, deltaF508; exon 11: G542X, S549N, G551D, R553X, A559T, R560K, R560T; exon 13: K716X, Q685X, G628R, L719X; exon 17b: H1054D, G1061R, 3320ins5, R1066H, R1066L, R1070Q, 3359delCT, L1077P, H1085R, Y1092X; exon 19: R1162X, 3659delC, 3662delA, 3667del4, 3737delA, I1234V, S1235R, 3849G>A; exon 20: 3860ins31,S1255X,3898insC,3905insT,D1270N, W1282X, Q1291R; and exon 21: N1303H, N1303K, W1316X.
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ABCC7 p.Asn1303Lys 11933191:42:714
status: NEW
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PMID: 11938439 [PubMed] Audrezet MP et al: "Determination of the relative contribution of three genes-the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene-to the etiology of idiopathic chronic pancreatitis."
No. Sentence Comment
56 `Gain-of-function' PRSS1 mutations are rare in ICP While PRSS1 mutations are often found in patients with hereditary pancreatitis, they can also be identified in subjects with ICP, albeit with an exceptionally low Table 1 Sequence variations identified in the PRSS1, PSTI, and CFTR genes in 39 patients with ICP CFTR Patient PRSS1 PSTI Mutant PolyT 1 ± a ± ± 7T/7T 2 ± ± F508del/R352Q 9T/7T 3 ± ± F508del/P5L 9T/7T 4 ± ± c.4575+2G4A 9T/7T 5 ± ± ± 7T/7T 6 ± N34Sb ± 7T/7T 7 ± ± ± 7T/5T 8 ± ± F508del/Q1476X 9T/7T 9 ± ± ± 7T/7T 10 ± ± ± 7T/7T 11 ± ± ± 7T/7T 12 ± ± ± 7T/7T 13 ± ± V562I 7T/5T 14 ± ± 2C4A W1282X 7T/5T 15 ± ± IVS3-6T4C 7T/7T 16 R122H ± ± 7T/7T 17 ± ± ± 9T/7T 18 ± ± ± 7T/5T 19 ± ± ± 7T/7T 20 ± N34S/N34S ± 7T/7T 21 ± ± ± 9T/5T 22 ± ± ± 7T/7T 23 ± ± E217G/A1136T 9T/7T 24 ± ± ± 7T/7T 25 ± ± ± NDc 26 ± ± ± ND 27 ± N34S IVS18 ± 20T4C 9T/7T 28 ± ± F508del 9T/7T 29 ± ± ± 7T/7T 30 ± ± N1303K ND 31 ± ± G542X 9T/7T 32 ± ± ± 7T/5T 33 ± ± F508del 9T/7T 34 ± ± 41G4Ad ± 7T/7T 35 ± ± ± 9T/7T 36 ± ± ± 9T/7T 37 ± ± ± 7T/7T 38 ± N34S L967S 7T/7T 39 ± ± ± 7T/5T a Indicates two wild alleles.
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ABCC7 p.Asn1303Lys 11938439:56:1274
status: NEW
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PMID: 11966405 [PubMed] Sangiuolo F et al: "Towards the pharmacogenomics of cystic fibrosis."
No. Sentence Comment
111 Gentamicin Neomicin (G418) Class II Mutations that fail to be properly processed to a matureglycosylatedform and transported to the apical membrane ∆F508 N1303K P574H A455E PI Defective CFTR processing and trafficking.
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ABCC7 p.Asn1303Lys 11966405:111:161
status: NEW
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PMID: 11994102 [PubMed] Eaton TE et al: "Cystic fibrosis transmembrane conductance regulator gene mutations: do they play a role in the aetiology of allergic bronchopulmonary aspergillosis?"
No. Sentence Comment
53 Cystic ®brosis mutation analysis Genomic DNA samples were screened for 16 CF mutations utilizing allelic-speci®c oligonucleotide (ASO) hybridization; ÁF508, ÁI507, R117H, W1282X, 621 ‡ IG3T, R334W, R347P, A455E, 1717-IG3A, G542X, 5549N, G551D, R553X, R560T, N1303K and 3849 ‡ 10KC3T.
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ABCC7 p.Asn1303Lys 11994102:53:283
status: NEW
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PMID: 12000363 [PubMed] Visich A et al: "Complete screening of the CFTR gene in Argentine cystic fibrosis patients."
No. Sentence Comment
35 Screening for DF508 and 12 other known mutations DF508 and 11 other frequent mutations (i.e. DI507, G551D, R553X, S549N, S549I, R1162X, 1811π1.6KbA»T, G542X, 1717-1G»A, 208 W1282X and N1303K) were detected as previously described (5).
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ABCC7 p.Asn1303Lys 12000363:35:200
status: NEW
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56 Frequency of cystic fibrosis transmembrane regulator mutations in the Argentine population: 440 chromosomes analysed Mutation Localization Chromosome Number Percentage DF508 Exon 10 258 58.64 G542X Exon 11 18 4.10 W1282X Exon 20 12 2.73 N1303K Exon 21 12 2.73 R334W Exon 7 5 1.14 1717-1G»A Intron 10 5 1.14 3849π10KbC»T Intron 19 4 0.91 1811π1.6KbA»G Intron 11 4 0.91 IVS8-5T Intron 8 4 0.91 G85E Exon 3 3 0.68 621π1G»T Intron 4 3 0.68 2789π5G»A Intron 14b 3 0.68 DI507 Exon 10 3 0.68 2184delA Exon 13 2 0.45 2566insT Exon 13 2 0.45 2686insT Exon 14a 2 0.45 3659delC Exon 19 2 0.45 R1162X Exon 19 2 0.45 4016insT Exon 21 2 0.45 2789π2insA Intron 14b 2 0.45 L6V Exon 1 1 0.23 297π2A»G Intron 2 1 0.23 W57X Exon 3 1 0.23 R75Q Exon 3 1 0.23 Q220X Exon 6a 1 0.23 Y362X Exon 7 1 0.23 D426C Exon 9 1 0.23 1460delAT Exon 9 1 0.23 1353insT Exon 9 1 0.23 1782delA Exon 11 1 0.23 R553X Exon 11 1 0.23 S549R Exon 11 1 0.23 1898π3A»G Intron 12 1 0.23 2594delGT Exon 13 1 0.23 2183AA»G Exon 13 1 0.23 I1027T Exon 17a 1 0.23 R1066C Exon 17b 1 0.23 G1061R Exon 17b 1 0.23 4005-1G»A Intron 20 1 0.23 Total 367 83.45 209 nificant differences were observed among the compared populations (Table2).
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ABCC7 p.Asn1303Lys 12000363:56:237
status: NEW
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83 Only five other mutations (i.e. G542X, W1282X, N1303K, 1717-1G»A and R334W) showed frequencies higher than 1%, while approximately half the mutations (49%) were rare since they were found in only one CF family.
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ABCC7 p.Asn1303Lys 12000363:83:47
status: NEW
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99 They have established the group of CF mutations (i.e. DF508, G542X, W1282X, N1303K, 1717-1G»A and R334W) that should be considered in screening programmes based on both IRT and DNA analysis to obtain at least 70% sensitivity.
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ABCC7 p.Asn1303Lys 12000363:99:78
status: NEW
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PMID: 12007216 [PubMed] Bobadilla JL et al: "Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with incidence data and application to screening."
No. Sentence Comment
101 Mutations that fall into this category include: 1) G542X, of single origin, associated with the ancient Phoenicians [Loirat et al., 1997], 2) N1303K, also of single origin, and linked to ancient Mediterranean populations, and 3) G551D, also of single origin [Cashman et al., 1995], having been associated with the ancient Celtic tribes [Macek et al., 1991].
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ABCC7 p.Asn1303Lys 12007216:101:142
status: NEW
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109 Mutational Arrays, Detection Rates and Methods by Region* Estimated Projected detection of Number of Number of Country/ allele two CFTR mutations chromosomes Region Mutation array detectiona mutationsb includedc (max/min)d Reference Europe Albania ∆F508 (72.4%) C276X (0.7%) 74.5 55.5 4 270/146 CFGAC [1994]; Macek et al. G85E (0.7%) R1070Q (0.7%) [2002] Austria ∆F508 (62.9%) 457TAT→G (1.2%) 76.6 58.7 11 1516/580 Estiville et al. [1997]; Dörk et al. (total) G542X (3.3%) 2183AA→G (0.7%) [2000]; Macek et al. [2002] CFTRdele2,3 (2.1%) N1303K (0.6%) R1162X (1.9%) I148T (0.5%) R553X (1.7%) R117H (0.5%) G551D (1.2%) Austria ∆F508 (74.6%) 2183AA→G (2.4%) 95.3 90.8 8 126 Stuhrmann et al. [1997] (tyrol) R1162X (8.7%) G551D (1.6%) G542X (2.4%) R347P (1.6%) 2789+5G→A (2.4%) Q39X (1.6%) Belarus ∆F508 (61.2%) R553X (0.5%) 75.2 56.6 9 278/188 Dörk et al. [2000]; Macek et al. G542X (4.5%) R334W (0.5%) [2002] CFTRdele2,3 (3.3%) R347P (0.5%) N1303K (3.2%) S549N (0.5%) W1282X (1.0%) Belgium ∆F508 (75.1%) 622-1A→C (0.5%) 100.0 100.0 27 1504/522 Cuppens et al. [1993]; Mercier et G542X (3.5%) G458V (0.5%) al. [1993]; CFGAC [1994]; N1303K (2.7%) 1898+G→C (0.5%) Estivill et al.[1997] R553X (1.7%) G970R (0.5%) 1717-1G→A (1.6%) 4218insT (0.5%) E60X (1.6%) 394delTT (0.5%) W1282X (1.4%) K830X (0.5%) 2183A→G+2184delA (1.2%) E822K (0.5%) W401X (1.0%) 3272-1G→A (0.5%) A455E (1.0%) S1161R (0.5%) 3272-26A→G (1.0%) R1162X (0.5%) S1251N (1.0%) 3750delAG (0.5%) S1235R (0.8%) S1255P (0.5%) ∆I507 (0.6%) Bulgaria ∆F508 (63.6%) R75Q (1.0%) 93.0 86.5 21 948/432 Angelicheva et al. [1997]; (total) N1303K (5.6%) 2183AA→G (0.9%) Estivill et al. [1997]; Macek G542X (3.9%) G1244V+S912L (0.9%) et al. [2002] R347P (2.2%) G85E (0.9%) 1677delTA (2.1%) 2184insA (0.9%) R1070Q (1.8%) L88X+G1069R (0.8%) Q220X (1.2%) 2789+5G→A (0.8%) 3849+10KbC→T (1.1%) G1244E (0.8%) W1282X (1.0%) 1717-1G→A (0.8%) 2176insC (1.0%) Y919C (0.7%) G1069R (1.0%) WORLDWIDEANALYSISOFCFTRMUTATIONS581 Bulgaria 1) DF508 4) 1677delTA - - 6 13 Angelicheva et al. [1997] (ethnic 2) R347P 5) Q493R Turks) 3) G542X 6) L571S - - 1 30 Angelicheva et al. [1997] Bulgaria 1) DF508 (100.0%) (Gypsy) Croatia ∆F508 (64.5%) G551D (1.1%) 72.5 52.6 5 276 Macek et al. [2002] G542X (3.3%) 3849+10KbC→T (0.7%) N1303K (2.9%) Czech ∆F508 (70.0%) 1898+1G→T (2.0%) 89.6 80.3 10 2196/628 CFGAC [1994]; Estiville et al. Republic CFTRdele2,3 (5.5%) 2143delT (1.2%) [1997]; Dörk et al. [2000]; G551D (3.8%) R347P (0.8%) Macek et al. [2002] N1303K (2.9%) 3849+10KbC→T (0.6%) G542X (2.2%) W1282X (0.6%) Denmark ∆F508 (87.5%) G542X (0.7%) 92.3 85.2 6 1888/678 CFGAC [1994]; Schwartz et al. (excluding 394delTT (1.8%) 621+1G→T (0.6%) [1994]; Estiville et al. [1997] Faroe) N1303K (1.1%) 3659delC (0.6%) Estonia ∆F508 (51.7%) R117C (1.7%) 80.2 64.3 10 165/80 Estivill et al. [1997]; Klaassen et 394delTT (13.3%) E217G (1.7%) al. [1998]; Macek et al. S1235R (3.3%) R1066H (1.7%) [2002] 359insT (1.7%) 3659delC (1.7%) I1005R (1.7%) S1169X (1.7%) Finland ∆F508 (46.2%) G542X (1.9%) 78.8 62.1 4 132/52 CFGAC [1994]; Kere et al. 394delTT (28.8%) 3372delA (1.9%) [1994]; Estivill et al. [1997] France ∆F508 (67.7%) 2789+5G→T (0.79%) 79.7 63.6 12 17854/7420 Chevalier-Porst et al. [1994]; (total) G542X (2.94%) 2184delA+2183A→G (0.77%) Estivill et al. [1997]; Claustres et al. [2000]; Guilloud-Bataille N1303K (1.83%) G551D (0.74%) et al. [2000] 1717-1G→A (1.35%) 1078delT (0.63%) W1282X (0.91%) ∆I507 (0.62%) R553X (0.86%) Y122K (0.59%) France ∆F508 (75.8%) R297Q (0.8%) 98.7 97.4 18 599/365 Férec et al. [1992]; Scotet et al. (Brittany) 1078delT (4.0%) R347H (0.8%) [2000] G551D (3.6%) I1234V (0.8%) N1303K (3.0%) R553X (0.8%) R117H (1.7%) 2789+5G→A (0.8%) 3272-26A→G (1.3%) 4005+1G→A (0.7%) G542X (1.1%) 621+1G→T (0.6%) 1717-1G→A (1.0%) ∆I507 (0.6%) G1249R (0.8%) W846X (0.5%) France ∆F508 (70.0%) N1303K (0.8%) 90.4 81.7 16 250 Claustres et al. [1993] (southern) G542X (6.4%) 3737delA (0.8%) 1717-1G→A (1.6%) R1162X (0.8%) L206W (1.2%) Y1092X (0.8%) R334W (1.2%) S945L (0.8%) ∆I507 (1.2%) K710X (0.8%) 2184delA (1.2%) 1078delT (0.8%) R1158X (1.2%) Y122X (0.8%) (Continued) BOBADILLAETAL.
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ABCC7 p.Asn1303Lys 12007216:109:569
status: NEW
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ABCC7 p.Asn1303Lys 12007216:109:1003
status: NEW
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ABCC7 p.Asn1303Lys 12007216:109:1206
status: NEW
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ABCC7 p.Asn1303Lys 12007216:109:1710
status: NEW
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ABCC7 p.Asn1303Lys 12007216:109:2416
status: NEW
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ABCC7 p.Asn1303Lys 12007216:109:2657
status: NEW
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ABCC7 p.Asn1303Lys 12007216:109:2907
status: NEW
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ABCC7 p.Asn1303Lys 12007216:109:3564
status: NEW
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ABCC7 p.Asn1303Lys 12007216:109:3889
status: NEW
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ABCC7 p.Asn1303Lys 12007216:109:4137
status: NEW
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110 Germany ∆F508 (71.8%) 1789+5G→A (0.9%) 87.6 76.7 17 5662/1316 Dörk et al. [1992]; Dörk et al. R553X (2.0%) 3272-26A→G (0.9%) [1994]; Tümmler et al. [1996]; N1303K (1.8%) W1282X (0.7%) Estivill et al. [1997]; Dörk et G542X (1.2%) 2143delT (0.7%) al. [2000] R347P (1.2%) 1078delT (0.6%) CFTRdele2,3 (1.2%) 2183AA→G (0.6%) 3849+10KbC→T (1.0%) 2184insA (0.6%) G551D (0.9% 3659delC (0.6%) 1717-1G→A (0.9%) Greece ∆F508 (52.9%) 3272-26A→G (0.8%) 82.2 67.6 22 2097/718 Kanavakis et al. [1995]; Estivill 621+1G→T (5.0%) R1070Q (0.8%) et al. [1997]; Tzetis et al. G542X (4.1%) W496X (0.7%) [1997]; Macek et al. [2002] N1303K (3.3%) 621+3A→G (0.7%) 2183AA→G (1.8%) ∆I507 (0.7%) 2789+5G→A (1.7%) W1282X (0.7%) E822X (1.6%) 574delA (0.7%) R117H (1.2%) 1677delTA (0.7%) R334W (1.1%) A46D (0.6%) R1158X (1.0%) 3120+1G→A (0.6%) G85E (1.0%) G551D (0.5%) Hungary ∆F508 (54.9%) W1282X (1.8%) 68.3 46.6 9 1133/976 CFGAC [1994]; Estivill et al. 1717-1G→A (1.9%) G542X (1.7%) [1997]; Macek et al. [2002] R553X (2.1%) N1303K (1.3%) Y1092X (1.8%) G551D (1.0%) S1196X (1.8%) Ireland ∆F508 (70.4%) G542X (1.0%) 82.1 67.4 7 801/509 CFGAC [1994]; Estivill et al. G551D (5.7%) 621+1G→T (0.8%) [1994] R117H (2.4%) 1717-1G→A (0.6%) R560T (1.2%) Italy ∆F508 (50.9%) ∆I507 (0.65%) 60.3 36.4 9 3524 Estivill et al. [1997] (total) G542X (3.1%) W1282X (0.62%) 1717-1G→A (1.6%) Y122K (0.59%) N1303K (1.4%) G551D (0.53%) R553X (0.94%) Italy ∆F508 (47.6%) R553X (1.3%) 87.1 75.9 15 225 Bonizzato et al. [1995] (Northeast) R1162X (9.8%) 2789+G→A (1.3%) 2183AA→G (9.3%) Q552X (1.3%) N1303K (4.0%) 621+1G→T (0.9%) G542X (2.7%) W1282X (0.9%) 711+5G→A (2.7%) 3132delTG (0.9%) 1717-1G→A (2.2%) 2790-2A→G (0.9%) G85E (1.3%) TABLE 1. Continued. Estimated Projected detection of Number of Number of Country/ allele two CFTR mutations chromosomes Region Mutation array detectiona mutationsb includedc (max/min)d Reference WORLDWIDEANALYSISOFCFTRMUTATIONS583 Italy ∆F508 (56.4%) 711+1G→T (1.3%) 85.7 73.4 13 660/396 Castaldo et al. [1996]; Castaldo (southern) N1303K (6.8%) G1244E (1.3%) et al. [1999] G542X (5.7%) R1185X (1.3%) W1282X (3.8%) L1065P (1.3%) 1717-1G→A (2.3%) R553X (1.1%) 2183AA→G (1.9%) I148T (0.7%) 4016insT (1.8%) Latvia 1) DF508 (58.3%) 4) CFTRdele2,3 (2.8%) - - 6 36 Dörk et al. [2000]; Macek et al. 2) 3849+10KbC®T (8.3%) 5) W1282X (2.8%) [2002] 3) N1303K (5.6%) 6) 394delTT (2.8%) Lithuania ∆F508 (31.0%) N1303K (2.0%) 39.0 15.2 4 94 Dörk et al. [2000]; Macek et al. R553X (4.0%) CFTRdele2,3 (2.0%) [2002] Macedonia ∆F508 (54.3%) 711+3A→G (1.0%) 69.2 47.9 12 559/226 Petreska et al. [1998]; Dörk et G542X (4.2%) 3849G→A (1.0%) al. [2000]; Macek et al. N1303K (2.0%) 2184insA (0.9%) [2002] CFTRdele2,3 (1.3%) 457TAT→G (0.7%) 621+1G→T (1.3%) V139E (0.7%) 611-1G→T (1.2%) 1811+1G→C (0.6%) Netherlands ∆F508 (74.2%) R1162X (0.9%) 86.8 75.3 9 3167/1442 Gan et al. [1995]; Estiville et al. A455E (4.7%) S1251N (0.9%) [1997]; Collee et al. [1998] G542X (1.8%) N1303K (0.9%) 1717-1G→A (1.5%) W1282X (0.7%) R553X (1.2%) Norway ∆F508 (60.2%) G551D (1.2%) 69.8 48.7 6 410/242 Schwartz et al. [1994]; Estivill 394delTT (4.2%) G542X (0.6%) et al. [1997] R117H (3.0%) N1303K (0.6%) Poland ∆F508 (57.1%) CFTRdele2,3 (1.8%) 73.5 54.0 11 4046/1726 CFGAC [1994]; Estivill et al. 3849+10Kb C→T (2.7%) R560T (1.5%) [1997]; Dörk et al [2000]; G542X (2.6%) W1282X (0.7%) Macek et al. [2002] 1717-1G→A (2.4%) ∆I507 (0.5%) R553X (1.9%) G551D (0.5%) N1303K (1.8%) Portugal ∆F508 (44.7%) R334W (0.7%) 49.7 24.7 5 739/454 CFGAC [1994]; Estivill et al. G542X (1.6%) N1303K (0.7%) [1997] R1066C (2.0%) Romania ∆F508 (36.6%) G542X (1.4%) 51.5 26.5 11 224/74 CFGAC [1994]; Estivill et al. 2043delG (2.0%) R553X (1.4%) [1997]; Popa et al. [1997]; W1282X (1.7%) G576X (1.4%) Macek et al. [2002] 1717-2A→G (1.4%) 1898+1G→A (1.4%) I148T (1.4%) 2183AA→G (1.4%) 621+1G→T (1.4%) Russia ∆F508 (54.4%) 552insA (0.9%) 70.7 50.0 12 5073/2562 CFGAC [1994]; Estivill et al. CFTRdele2,3 (5.0%) G542X (0.9%) [1997]; Dörk et al. [2000]; R553X (3.5%) R334W (0.9%) Macek et al. [2002] 2183AA→G (1.3%) 1677delTA (0.8%) W1282X (1.0%) Y122X (0.5%) 394delTT (1.0%) 1367del5 (0.5%) (Continued) BOBADILLAETAL.
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ABCC7 p.Asn1303Lys 12007216:110:192
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:692
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:1128
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:1530
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:1738
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:2249
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:2583
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:2647
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:2925
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:3261
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:3476
status: NEW
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ABCC7 p.Asn1303Lys 12007216:110:3780
status: NEW
X
ABCC7 p.Asn1303Lys 12007216:110:3900
status: NEW
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111 Slovakia ∆F508 (57.3%) CFTRdele2,3 (1.2%) 82.7 68.4 14 908/254 CFGAC [1994]; Estivill et al. G542X (6.8%) 3849+10KbC→T (1.0%) [1997]; Dörk et al. [2000]; R553X (4.0%) S42F (0.9%) Macek et al. [2002] N1303K (3.4%) R75X (0.9%) 2143delT (1.8%) G85E (0.9%) R347P (1.4%) 605insT (0.9%) W1282X (1.3%) 1898+1G→A (0.9%) Slovenia ∆F508 (57.8%) R347P (1.1%) 79.7 63.5 16 455/132 CFGAC [1994]; Dörk et al. 2789+5G→A (4.1%) S4X (0.8%) [2000]; Macek et al. [2002] R1162X (3.2%) 457TAT→G (0.8%) G542X (1.9%) D192G (0.8%) Q552X (1.5%) R553X (0.8%) Q685X (1.5%) A559T (0.8%) 3905insT (1.5%) 2907delTT (0.8%) CFTRdele2,3 (1.5%) 3667ins4 (0.8%) Spain ∆F508 (52.7%) G85E (0.8%) 80.2 64.3 21 3608/1356 Chillón et al. [1994]; Casals et G542X (8.0%) R1066C (0.8%) al. [1997]; Estivill et al. [1997] N1303K (2.5%) 2789+5G→A (0.7%) 3601-111G→C (2.0%) 2869insG (0.7%) 1811+1.6Kb A→G (1.7%) ∆I507 (0.6%) R1162X (1.6%) W1282X (0.6%) 711+1G→T (1.3%) L206W (0.5%) R334W (1.2%) R709X (0.5%) Q890X (1.0%) K710X (0.5%) 1609delCA (1.0%) 3272-26A→G (0.5%) 712-1G→T (1.0%) Sweden ∆F508 (66.6%) E60X (0.6%) 85.9 73.8 10 1357/662 Schwartz et al. [1994]; Estivill et 394delTT (7.3%) Y109C (0.6%) al. [1997]; Schaedel et al. 3659delC (5.4%) R117H (0.6%) [1999] 175insT (2.4%) R117C (0.6%) T338I (1.2%) G542X (0.6%) Switzerland ∆F508 (57.2%) K1200E (2.1%) 91.3 83.4 9 1268/1173 Estivill et al. [1997]; R553X (14.0%) N1303K (1.2%) Hergersberg et al. [1997] 3905insT (9.8%) W1282X (1.1%) 1717-1G→A (2.7%) R347P (0.6%) G542X (2.6%) Ukraine ∆F508 (65.2%) CFTRdele2,3 (1.1%) 74.6 55.7 6 1055/580 Estivill et al. [1997]; Dörk et al. R553X (3.6%) G551D (1.8%) [2000]; Macek et al. [2002] N1303K (2.4%) W1282X (0.5%) United ∆F508 (75.3%) 621+1G→T (0.93%) 81.6 66.6 5 19622/9815 Schwartz et al. [1995b]; Kingdom G551D (3.1%) 1717-1G→A (0.57%) Estivill et al. [1997] (total) G542X (1.7%) TABLE 1. Continued. Estimated Projected detection of Number of Number of Country/ allele two CFTR mutations chromosomes Region Mutation array detectiona mutationsb includedc (max/min)d Reference WORLDWIDEANALYSISOFCFTRMUTATIONS585 United ∆F508 (56.6%) 621+1G→T (1.8%) 69.1 47.7 7 456 CFGAC [1994] Kingdom G551D (3.7%) R117H (1.5%) (N. Ireland) R560T (2.6%) ∆I507 (0.9%) G542X (2.0%) United ∆F508 (19.2%) 621+2T→C (3.8%) 84.4 71.2 11 52 Malone et al. [1998] Kingdom Y569D (15.4%) 2184insA (3.8%) (Pakistani) Q98X (11.5%) R560S (1.9%) 1525-1G→A (9.6%) 1898+1G→T (1.9%) 296+12T→C (7.7%) R709X (1.9%) 1161delC (7.7%) United ∆F508 (71.3%) 1717-1G→A (1.0%) 86.4 74.6 9 1236/730 Shrimpton et al. [1991]; Kingdom G551D (5.5%) 621+1G→T (0.6%) Gilfillan et al. [1998] (Scotland) G542X (4.0%) ∆I507 (0.6%) R117H (1.4%) R560T (0.6%) P67L (1.4%) United ∆F508 (71.6%) 1717-1G→A (1.1%) 98.7 97.4 17 183 Cheadle et al. [1993] Kingdom 621+1G→T (6.6%) 3659delC (0.5%) (Wales) 1898+1G→A (5.5%) R117H (0.5%) G542X (2.2%) N1303K (0.5%) G551D (2.2%) E60X (0.5%) 1078delT (2.2%) S549N (0.5%) R1283M (1.6%) 3849+10KbC→T (0.5%) R553X (1.1%) 4016insT (0.5%) ∆I507 (1.1%) Yugoslavia ∆F508 (68.9%) 3849G→A (1.0%) 82.2 67.6 11 709/398 Dabovic et al. [1992]; Estivill et G542X (4.0%) N1303K (0.8%) al. [1997]; Macek et al. R1162C (3.0%) 525delT (0.5%) (submitted for publication) 457TAT→G (1.0%) 621+1G→T (0.5%) I148T (1.0%) G551D (0.5%) Q552X (1.0%) Middle East/Africa Algeria 1) DF508 (20.0%) 4) 1812-1G®A (5.0%) - - 5 20 Loumi et al. [1999] 2) N1303K (20.0%) 5) V754M (5.0%) 3) 711+1G®T (10.0%) Jewish W1282X (48.0%) 3849+10KbC→T (6.0%) 95.0 90.3 6 261 Kerem et al. [1995] (Ashkenazi) ∆F508 (28.0%) N1303K (3.0%) G542X (9.0%) 1717-1G→A (1.0%) Jewish 1) N1303K - - 1 6 Kerem et al. [1995] (Egypt) Jewish 1) Q359K/T360K - - 1 8 Kerem et al. [1995] (Georgia) Jewish 1) DF508 2) 405+1G®A - - 2 11 Kerem et al. [1995] (Libya) Jewish 1) DF508 (72.0%) 3) D1152H (6.0%) - - 3 33 Kerem et al. [1995] (Morocco) 2) S549R (6.0%) Jewish ∆F508 (35.0%) W1282X (2.0%) 43.0 18.5 4 51 Shoshani et al. [1992] (Sepharadim) G542X (4.0%) S549I (2.0%) (Continued) BOBADILLAETAL.
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ABCC7 p.Asn1303Lys 12007216:111:218
status: NEW
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ABCC7 p.Asn1303Lys 12007216:111:841
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ABCC7 p.Asn1303Lys 12007216:111:1503
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ABCC7 p.Asn1303Lys 12007216:111:1787
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ABCC7 p.Asn1303Lys 12007216:111:3119
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ABCC7 p.Asn1303Lys 12007216:111:3400
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ABCC7 p.Asn1303Lys 12007216:111:3682
status: NEW
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ABCC7 p.Asn1303Lys 12007216:111:3856
status: NEW
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ABCC7 p.Asn1303Lys 12007216:111:3917
status: NEW
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112 Jewish 1) 405+1G®A (48.0%) 3) W1282X (17.0%) - - 4 23 Kerem et al. [1995] (Tunisia) 2) DF508 (31.0%) 4) 3849+10KbC®T (4.0%) Jewish 1) G85E 4) G542X - - 6 10 Kerem et al. [1995] (Turkey) 2) DF508 5) 3849+10KbC®T 3) W1282X 6) W1089X Jewish (Yemen) None - - 0 5 Kerem et al. [1995] Lebanon 1) DF508 (35.0%) 6) 4096-28G®A (2.5%) - - 9 40 Desgeorges et al. [1997] 2) W1282X (20.0%) 7) 2789+5G®A (2.5%) 3) 4010del4 (10.0%) 8) M952I (2.5%) 4) N1303K (10.0%) 9) E672del (2.5%) 5) S4X (5.0%) Reunion ∆F508 (52.0%) 1717-1G→A (0.7%) 90.4 81.7 9 138 Cartault et al. [1996] Island Y122X (24.0%) G542X (0.7%) 3120+1G→A (8.0%) A309G (0.7%) A455E (2.2%) 2789+5G→A (0.7%) G551D (1.4%) Saudi North: 3) H139L - - North 1 49 families El-Harith et al. [1997]; Arabia 1) 1548delG 4) L1177X Central 3 Kambouris et al. [1997]; Central: 5) DF508 South 4 Banjar et al. [1999] 1)I1234V 6) 3120+1G®A West 9 2)1548delG 7) 425del42 East 6 3)DF508 8) R553X South: 9) N1303K 1) I1234V East: 2) 1548delG 1) 3120+1G®A 3) 711+1G®T 2) H139L 4) 3120+1G®A 3) 1548delG West: 4) DF508 1) I1234V 5) S549R 2) G115X 6) N1303K Tunisia ∆F508 (17.6%) G85E (2.6%) 58.7 34.5 11 78 Messaoud et al. [1996] G542X (8.9%) W1282X (2.6%) 711+1G→T (7.7%) Y122X (1.3%) N1303K (6.4%) T665S (1.3%) 2766del8NT (6.4%) R47W+D1270N (1.3%) R1066C (2.6%) Turkeye ∆F508 (24.5%) 1066L (1.3%) 80.6 65.0 36 1067/670 Yilmaz et al. [1995]; Estivill et al. 1677delTA (4.1%) E822X (1.3%) [1997]; Onay et al. [1998]; 2789+5G→A (3.9%) 2183+5G→A+2184insA (1.3%) Macek et al. [2002] 2181delA (3.8%) D110H (0.8%) R347H (3.6%) P1013L (0.8%) N1303K (2.9%) 3172delAC (0.8%) 621+1G→T (2.6%) 1259insA (0.8%) G542X (2.6%) M1028I (0.8%) TABLE 1. Continued. Estimated Projected detection of Number of Number of Country/ allele two CFTR mutations chromosomes Region Mutation array detectiona mutationsb includedc (max/min)d Reference WORLDWIDEANALYSISOFCFTRMUTATIONS587 E92K (2.6%) 4005+1G→A (0.7%) A96E (2.6%) W1282X (0.7%) M152V (2.6%) I148T (0.6%) 2183AA→G (2.5%) R1162X (0.6%) 296+9A→T (1.6%) D1152H (0.6%) 2043delG (1.4%) W1098X (0.6%) E92X (1.4%) E831X (0.6%) K68N (1.4%) W496X (0.6%) G85E (1.3%) F1052V (0.5%) R1158X (1.3%) L571S (0.5%) United Arab S549R (61.5%) ∆F508 (26.9%) 88.4 78.1 2 86/52 Frossard et al. [1988]; Emirates Frossard et al. [1999] North/Central/South Americas Argentina ∆F508 (58.6%) N1303K (1.8%) 69.1 47.7 5 326/228 CFGAC [1994]; Chertkoff et al. W1282X (3.9%) 1717-1G→A (0.9%) [1997] G542X (3.9%) Brazilf ∆F508 (47.7%) W1282X (1.3%) 66.8 44.6 10 820/500 CFGAC [1994]; Cabello et al. (total) G542X (7.2%) G85E (1.3%) [1999]; Raskin et al. [1999]; R1162X (2.5%) R553X (0.7%) Bernardino et al. [2000] R334W (2.5%) L206W (0.6%) N1303K (2.4%) 2347delG (0.6%) South East: >∆F508, G542X South: >N1303K Brazil ∆F508 (31.7%) N1303K (2.5%) 42.5 18.1 3 120 Parizotto and Bertuzzo [1997] (Sao Paulo) G542X (8.3%) Canada ∆F508 (59.0%) G542X (0.5%) 98.5 97.0 13 381/200 Rozen et al. [1992]; (Lac St. Jean) 621+1G→T (24.3%) N1303K (0.5%) De Braekeleer et al. [1998] A445E (8.2%) Q890X (0.5%) Y1092X (1.2%) S489X (0.5) 711+1G→T (1.0%) R117C (0.5%) I148T (1.0%) R1158 (0.5%) G85E (0.8%) Canada ∆F508 (71.4%) ∆I507 (1.3%) 90.9 82.6 7 77 Rozen et al. [1992] (Quebec City) 711+1G→T (9.1%) Y1092X (1.3%) 621+1G→T (5.2%) N1303K (1.3%) A455E (1.3%) Canada ∆F508 (70.9%) W1282X (0.9%) 82.0 67.2 10 632 Kristidis et al. [1992] (Toronto) G551D (3.1%) R117H (0.9%) G542X (2.2%) 1717-1G→A (0.6%) 621+1G→T (1.3%) R560T (0.6%) N1303K (0.9%) ∆I507 (0.6%) Chile ∆F508 (29.2%) R553X (4.2%) 33.4 11.2 2 72 Rios et al. [1994] Columbia 1) DF508 (35.4%) 3) N1303K (2.1%) - - 4 48 Restrepo et al. [2000] 2) G542X (6.3%) 4) W1282X (2.1%) Ecuador 1) DF508 (25%) - - 1 20 Paz-y-Mino et al. [1999] (Continued) BOBADILLAETAL.
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ABCC7 p.Asn1303Lys 12007216:112:461
status: NEW
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ABCC7 p.Asn1303Lys 12007216:112:994
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ABCC7 p.Asn1303Lys 12007216:112:1149
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ABCC7 p.Asn1303Lys 12007216:112:1299
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ABCC7 p.Asn1303Lys 12007216:112:1670
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ABCC7 p.Asn1303Lys 12007216:112:2475
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ABCC7 p.Asn1303Lys 12007216:112:2832
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ABCC7 p.Asn1303Lys 12007216:112:2938
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ABCC7 p.Asn1303Lys 12007216:112:3145
status: NEW
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ABCC7 p.Asn1303Lys 12007216:112:3470
status: NEW
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ABCC7 p.Asn1303Lys 12007216:112:3689
status: NEW
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ABCC7 p.Asn1303Lys 12007216:112:3826
status: NEW
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113 Mexico ∆F508 (41.6%) G551S (0.5%) 75.5 57.0 35 374/194 Orozco et al.[1993]; Villalobos- G542X (5.6%) 1078delT (0.5%) Torres et al. [1997]; Liang et al. ∆I507 (2.5%) Y1092X (0.5%) [1998]; Orozco et al. [2000] S549N (1.9%) R117H (0.5%) N1303K (1.7%) G85E (0.5%) R75X (1.5%) 1716G→A (0.5%) 406-1G→A (1.5%) W1204X (0.5%) I148T (1.5%) W1098C (0.5%) 3849+10KbC→T (1.5%) 846delT (0.5%) 621+1G→T (1.2%) P750L (0.5%) 2055del9→A (1.0%) V754M (0.5%) 935delA (1.0%) R75Q (0.5%) I506T (1.0) W1096X (0.5%) 3199del6 (1.0%) L558S (0.5%) 2183AA→G (1.0%) 4160insGGGG (0.5%) G551D (0.5%) 297-1G→A (0.5%) R553X (0.5%) H199Y (0.5%) 1924del7 (0.5%) United States ∆F508 (68.6%) R553X (0.9%) 79.7 63.5 10 25048 Cystic Fibrosis Foundation (total) G542X (2.4%) 621+1G→T (0.9%) [1998] G551D (2.1%) 1717-1G→A (0.7%) W1282X (1.4%) 3849+10KbC→T (0.7%) N1303K (1.3%) R117H (0.7%) United States ∆F508 (48.0%) S1255X (1.4%) 77.3 59.8 16 160/148 Carles et al. [1996]; Macek et al. (African 3120+1G→A (12.2%) 444delA (0.7%) [1997]; Dörk et al. [1998]; American) 2307insA (2.0%) R334W (0.7%) Friedman et al. [1998] A559T (2.0%) ∆I507 (0.7%) R553X (2.0%) 1717-1G→A (0.7%) ∆F311 (2.0%) G542X (0.7%) G480C (1.4%) S549N (0.7%) 405+3A→C (1.4%) G551D (0.7%) United States 1) L1093P - - 1 2 Yee et al. [2000] (Cherokee) United States Non-French: French: Non- Non- Non- Non- Bayleran et al. [1996] (Maine) ∆F508 (82.0%) ∆F508 (58%) French: French: French: French: G542X (2.6%) 711+1G→T (8.3%) 95.3 90.8 11 191 G551D (2.6%) I148T (4.2%) French: French: French: French: N1303K (2.1%) A455E (4.2%) 80.3 64.5 8 72 R560T (1.0%) 1717-1G→A (1.4%) Total: 621+1G→T (1.0%) G85E (1.4%) 263 711+1G→T (1.0%) 621+1G→T (1.4%) R117H (1.0%) Y1092X (1.4%) 1717-1G→A (1.0%) G85E (0.5%) W1282X (0.5%) TABLE 1. Continued. Estimated Projected detection of Number of Number of Country/ allele two CFTR mutations chromosomes Region Mutation array detectiona mutationsb includedc (max/min)d Reference WORLDWIDEANALYSISOFCFTRMUTATIONS589 United States ∆F508 (46.0%) R334W (1.6%) 58.5 34.2 7 129 Grebe et al. [1994] (SW Hispanic) G542X (5.4%) W1282X (0.8%) 3849+10KbC→T (2.3%) R553X (0.8%) R1162X (1.6%) United States 1) R1162X - - 3 17 Mercier et al. [1992] (SW Native 2) D648V American) 3) G542X United States 1) R1162X 3) G542X - - 4 16 Mercier et al. [1994] (Zuni Pueblo) 2) 3849+10KbC®T 4) D648V Venezuela ∆F508 (29.6%) G542X (3.7%) 33.3 11.1 2 54 Restrepo et al. [2000] Other Regions Australia ∆F508 (76.9%) 621+1G→T (1.1%) 88.7 78.7 8 761/464 CFGAC [1994] G551D (4.5%) N1303K (0.9%) G542X (2.8%) W1282X (0.6%) R553X (1.3%) R117H (0.6%) East Asia 1) 1898+1G®T 2) 1898+5G®T - - 2 28 Suwanjutha et al. [1998] Hutterite 1) M1101K (69.0%) 2) DF508 (31.0%) - - 2 32 Zielenski et al. [1993] Brethren New Zealand ∆F508 (78.0%) N1303K (1.9%) 87.4 76.4 5 636 CFGAC [1994] G551D (4.4%) 621+1G→T (1.1%) G542X (2.0%) *This table presents the mutation panels for all regions investigated in this study.
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ABCC7 p.Asn1303Lys 12007216:113:248
status: NEW
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ABCC7 p.Asn1303Lys 12007216:113:913
status: NEW
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ABCC7 p.Asn1303Lys 12007216:113:1683
status: NEW
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ABCC7 p.Asn1303Lys 12007216:113:2740
status: NEW
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ABCC7 p.Asn1303Lys 12007216:113:3007
status: NEW
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169 The mutation N1303K is another CFTR allele that has a similar distribution patterns as G542X, and may also have been introduced via the Mediterranean route (Table 1).
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ABCC7 p.Asn1303Lys 12007216:169:13
status: NEW
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193 The top 10 list for the United States (Table 1) includes five CFTR alleles found in populations with distinct ethnic ancestries, i.e., G542X, G551D, W1282X, N1303K, and 3849+10KbC→T.
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ABCC7 p.Asn1303Lys 12007216:193:157
status: NEW
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213 Ideal Recommended CFTR Mutation Screening Panel for 2001 Neonatal Screening in the USA* Location Estimated Mutation in CFTRa percentageb Reason for inclusion DF508 Exon 10 68.6% CFF registry, >1%, Pan-European G542X Exon 11 2.4% CFF registry, >1%, Mediterranean G551D Exon 11 2.1% CFF registry, >1%, Celtic W1282X Exon 20 1.4% CFF registry, >1%, Ashkenazi Jew N1303K Exon 21 1.3% CFF registry, >1%, Mediterranean R553X Exon 11 0.9% CFF registry, >0.5%, Hispanic 621+1G®T Intron 4 0.9% CFF registry, >0.5%, multi-ethnic 1717-1G®A Intron 10 0.7% CFF registry, >0.5%, Italian 3849+10KbC®T Intron 19 0.7% CFF registry, >0.5%, Hispanic R117Hc Exon 4 0.7% CFF registry, >0.5% 1898+1G→T Intron 12 0.4% CFF registry, >0.1%, East Asian DI507 Exon 10 0.3% CFF registry, >0.1%, Hispanic 2789+5G®A Intron 14b 0.3% CFF registry, >0.1% G85E Exon 3 0.3% CFF registry, >0.1% R347P Exon 7 0.2% CFF registry, >0.1% R334W Exon 7 0.2% CFF registry, >0.1%, multi-ethnic R1162X Exon 19 0.2% CFF registry, >0.1%, multi-ethnic R560T Exon 11 0.2% CFF registry, >0.1% 3659delC Exon 19 0.2% CFF registry, >0.1% A455E Exon 9 0.2% CFF registry, >0.1% 2184delA Exon 13 0.1% CFF registry, >0.1% S549N Exon 11 0.1% CFF registry, >0.1%, multi-ethnic 711+1G®T Intron 5 0.1% CFF registry, >0.1% R75X Exon 3 0.2% Hispanic 406-1G→A Intron 3 0.2% Hispanic I148T Exon 4 0.2% Hispanic, French 2055del9→A Exon 13 0.1% Hispanic 935delA Exon 6b 0.1% Hispanic I506T Exon 10 0.1% Hispanic 3199del6 Exon 17a 0.1% Hispanic 2183AA→G Exon 13 0.1% Hispanic 3120+1G®A Intron 16 1.5% African American, Arabian 2307insA Exon 13 0.2% African American A559T Exon 11 0.2% African American ∆F311 Exon 7 0.2% African American G480C Exon 10 0.2% African American 405+3A→C Intron 3 0.2% African American S1255X Exon 20 0.2% African American L1093P Exon 17b Undetermined Native American D648V Exon 13 Undetermined Native American I1234V Exon 19 Undetermined Arabian linkage S549R Exon 11 Undetermined Arabian linkage 1898+5G→T Intron 12 Undetermined East Asian linkage CFTRdele2,3 Exons 2,3 Undetermined Eastern European linkage (Slavic) Y1092X Exon 17b Undetermined French linkage 394delTT Exon 3 Undetermined Nordic linkage Y569D Exon 12 Undetermined Pakistani linkage 3905insT Exon 20 Undetermined Swiss linkage (also: Amish, Acadian, Mennonite) 1898+1G®A Intron 12 Undetermined Welsh linkage M1101k Exon 17b Undetermined Hutterite ancestry *This table presents the top 50 mutations in the USA based on the Cystic Fibrosis Foundation CF Registry data from 1997 [Cystic Fibrosis Foundation, 1998], and data generated during our investigation.
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ABCC7 p.Asn1303Lys 12007216:213:360
status: NEW
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PMID: 12089190 [PubMed] Wang X et al: "Development and evaluation of a PCR-based, line probe assay for the detection of 58 alleles in the cystic fibrosis transmembrane conductance regulator (CFTR) gene."
No. Sentence Comment
68 Amplicon Size, bp Mutations (polymorphisms) Exon 13 598 2307 insA Intron 8, exon 09 548 A455E, 5T (7/9 T polymorphism) Exon 10 482 G480C, ⌬I507, ⌬F508 (F508C, I507V, I506V polymorphisms) Intron 10, exon 11 433 1717-1G3A, G542X, G551D, R553X, A559T, R560T Exon 19 420 R1162X, 3659delC Exon 21 397 N1303K Exon 20 359 S1255X, W1282X Exon 07 328 1078delT, R334W, R347P Exon 04, intron 4 288 R117H, 621ϩ1G3T Intron 14b 248 2789ϩ5G3A Intron 19 237 3849ϩ10kbC3T Exon 03 210 G85E, 405ϩ3A3C Intron 5 166 711ϩ1G3T Intron 16 139 3120ϩ1G3A Clinical Chemistry 48, No.
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ABCC7 p.Asn1303Lys 12089190:68:310
status: NEW
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88 The genotypes of each sample are as follows: lane 1, ϩ/ϩ (ϩ is the wild type); lane 2, 5T, R117H/3659delC; lane 3, G542X/ϩ; lane 4, I506V/ϩ; lane 5, I507V/ϩ; lane 6, F508C/⌬F508; lane 7, G85E/⌬F508; lane 8, 405ϩ3A3C/3120ϩ1G3C; lane 9, R117H/ϩ; lane 10, 621ϩ1G3T/⌬F508; lane 11, 711ϩ1G3T/⌬F508; lane 12, 1078delT/ϩ; lane 13, R334W/⌬F508; lane 14, R347P/⌬F508; lane 15, A455E/ϩ; lane 16, G480C/⌬F508; lane 17, ⌬I507/ϩ; lane 18, ⌬F508/ϩ; lane 19, 1717-1G3A/ϩ; lane 20, G542X/ϩ; lane 21, G551D/⌬F508; lane 22, R553X/ϩ; lane 23, R560T/⌬F508; lane 24, G551D/A559T; lane 25, 2307insA/ϩ; lane 26, 2789ϩ5G3A/⌬F508; lane 27, 3120ϩ1G3A/⌬F508; lane 28, R1162X/R1162X; lane 29, 3659delC/⌬F508; lane 30, 3849ϩ10kbC3T/⌬F508; lane 31, S1255X/⌬F508; lane 32, W1282X/G542X; lane 33, N1303K/ϩ.
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ABCC7 p.Asn1303Lys 12089190:88:1009
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PMID: 12116247 [PubMed] Muller F et al: "Predicting the risk of cystic fibrosis with abnormal ultrasound signs of fetal bowel: results of a French molecular collaborative study based on 641 prospective cases."
No. Sentence Comment
47 A, N1303K, W1282X), oligonucleotide ligation assay with the CF-OLA kit (PE-Biosystems, Foster City, CA) (31 mutations detected: DF508, DI507, Q493X, V520F, 1717-1G !
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ABCC7 p.Asn1303Lys 12116247:47:3
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50 G, R1162X, 3659delC, W1282X, 3905insT, N1303K, G85E, 621 þ 1G !
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ABCC7 p.Asn1303Lys 12116247:50:39
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PMID: 12124706 [PubMed] Orgad S et al: "Hyperechogenic bowel loops and meconium ileus in a fetus carrying the D1152H and G542X cystic fibrosis CFTR mutations."
No. Sentence Comment
21 Ashkenazi Jews were tested in the past only for F508del, W1282X, G542X, N1303K and 3849+10KbC>T of the cystic fibrosis transmembrane conductance regulator (CFTR) gene (Kerem et al., 1995, 1997; Abeliovich et al., 1992, 1996).
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ABCC7 p.Asn1303Lys 12124706:21:72
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PMID: 12133923 [PubMed] Corbetta C et al: "Screening for cystic fibrosis in newborn infants: results of a pilot programme based on a two tier protocol (IRT/DNA/IRT) in the Italian population."
No. Sentence Comment
266 Mutations identified by the assay are G85E, 621+1G→T, R117H, Y122X, 711+1G→T, 1078delT, R347P, R347H, R334W, A455E, 1898+1G→A, 2183-AA→G, 2789+5G→A, delF508, I507del, Q493X, V520F, 1717-1G→A, G542X, G551D, R553X, R560T, S549R, S549N, 3849+10kbC→T, 3849+4A→G, R1162X, 3659delC, W1282X, 3905insT, and N1303K.
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ABCC7 p.Asn1303Lys 12133923:266:355
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280 Genotypes are shown in table 1: 18% of our patients were delF508 homozygotes, 15% were homozygotes for other CFTR alleles (N1303K, 2183AA→G, 1717-1G→A, R334W, G542X), 21% were compound heterozygotes, and a further 43% were heterozygotes.
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ABCC7 p.Asn1303Lys 12133923:280:123
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285 The CFTR mutations identified and their frequencies among carriers were as follows: delF508 (72 chromosomes, 64.2%), N1303K (12, 10.7%), R117H (9, 8%), G542X (7, 6.25%), R347H, R1162X, 2789+5G→A (2 alleles each, 1.8%), 1898+1G→A, 1717-1G→A, W1282X, 2183-AA→G, 621+1G→T, and 3849+10kbC→T (1, 0.9%).
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ABCC7 p.Asn1303Lys 12133923:285:117
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310 Since 1998, in our CF centre, an expanded DNA CFTR gene analysis and repeat sweat test after 6-12 months of life have been performed in hypertrypsinaemic Table 1 Genotypes of 33 patients with CF identified in the 15 month period Two CFTR mutations identified (18 patients) by PCR/OLA: ∆F508/∆F508 6 N1303K/N1303K 2 ∆F508/N1303K 3 R334W/R334W 1 ∆F508/G542X 2 G542X/G542X 1 ∆F508/3659delC 1 2183AA→G/ 2183AA→G 1 ∆F508/R1162X 1 One CFTR mutation identified (13 patients) by PCR/OLA: ∆F508/D1152H* 1 ∆F508/Y1032C* 1 ∆F508/R1066H* 1 ∆F508/UN 6 ∆F508/R1066C* 1 W1282X/L1077P* 1 ∆F508/D579G* 1 G85E/UN 1 No CFTR mutation identified (two patients) by PCR/OLA: 711+3A→G*/UN 1 D110E*/D110E* 1 *CFTR alleles identified by analysis by denaturing gradient gel electrophoresis and sequencing.
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ABCC7 p.Asn1303Lys 12133923:310:313
status: NEW
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ABCC7 p.Asn1303Lys 12133923:310:320
status: NEW
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ABCC7 p.Asn1303Lys 12133923:310:342
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PMID: 12151438 [PubMed] Wang Z et al: "Analysis by mass spectrometry of 100 cystic fibrosis gene mutations in 92 patients with congenital bilateral absence of the vas deferens."
No. Sentence Comment
20 Given the frequency of CF mutations, especially in the Caucasian population ( in 25), and the common request by CBAVD men to sire their own offspring by using surgical Table I. The 100 most common cystic fibrosis mutations listed by exon Mutationa Exonb Frequency (%)c G85E 3 0.1 394delTT 3 Swedish E60X 3 Belgium R75X 3 405ϩ1G→A Int 3 R117H 4 0.30 Y122X 4 French 457TAT→G 4 Austria I148T 4 Canada (French Canadian) 574delA 4 444delA 4 R117L 4 621ϩ1G→T Int 4 0.72 711ϩ1G→T Int 5 Ͼ0.1 712-1G→T Int 5 711ϩ5G→A Int 5 Italy (Caucasian) L206W 6a R347P 7 0.24 1078delT 7 Ͼ0.1 R334W 7 Ͼ0.1 1154InsTC 7 T338I 7 Italy R347H 7 Turkey Q359K/T360K 7 Israel (Georgian Jews) I336K 7 R352Q 7 G330X 7 S364P 7 A455E 9 0.20 I507 10 0.21 F508 10 66.02 1609delCA 10 Spain (Caucasian) V520F 10 Q493X 10 C524X 10 G480C 10 Q493R 10 1717-1G→A Int 10 0.58 R553X 11 0.73 G551D 11 1.64 G542X 11 2.42 R560T 11 Ͼ0.1 S549N 11 Q552X 11 Italy S549I 11 Israel (Arabs) A559T 11 African American R553G 11 R560K 11 1812-1G→A Int 11 A561E 12 E585X 12 Y563D 12 Y563N 12 1898ϩ1G→A Int 12 0.22 1898ϩ1G→C Int 12 2183AA→G 13 Italian 2184delA 13 Ͻ0.1 K710X 13 2143delT 13 Moscow (Russian) 2184InsA 13 1949del84 13 Spain (Spanish) 2176InsC 13 2043delG 13 2307insA 13 2789ϩ5G→A Int 14b Ͼ0.1 2869insG 15 S945L 15 Q890X 15 3120G→A 16 2067 Table I. continued Mutationa Exonb Frequency (%)c 3120ϩ1G→A Int 16 African American 3272-26A→G Int 17a R1066C 17b Portugal (Portugese) L1077P 17b R1070Q 17b Bulgarian W1089X 17b M1101K 17b Canada (Hutterite) R1070P 17b R1162X 19 0.29 3659delC 19 Ͼ0.1 3849G→A 19 3662delA 19 3791delC 19 3821delT 19 Russian Q1238X 19 S1235R 19 France, South S1196X 19 K1177R 19 3849ϩ10kbC→T Int 19 0.24 3849ϩ4A→G Int 19 W1282X 20 1.22 S1251N 20 Dutch, Belgian 3905insT 20 Swiss, Acadian, Amish G1244E 20 R1283M 20 Welsh W1282R 20 D1270N 20 S1255X 20 African American 4005ϩ1G→A Int 20 N1303K 21 1.34 W1316X 21 aMutations were chosen according to their frequencies (Cystic Fibrosis Genetic Analysis Consortium, 1994; Zielenski and Tsui, 1995; Estivill et al., 1997).
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ABCC7 p.Asn1303Lys 12151438:20:2101
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34 The mutations in the 25 mutation panel were: ∆F508, G542X, N1303K, G551D, W1282X, 1717-1G→A, R553X, 621ϩ1G→T, R1162X, 2183AA→G, R117H, ∆I507, R560T, 3849ϩ10kbC→T, S549N, S549I, S549R, R1283M, R1283K, R553G, R560K, R117L, 1774delCT, 1811ϩ1G→C, and 4006-61del14.
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ABCC7 p.Asn1303Lys 12151438:34:66
status: NEW
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35 ACMG 25 mutation panel (ACMG25): The following mutations are the recommended core mutations for general population CF carrier screening by American College of Medical Genetics (ACMG) (Grody, et al 2001): ∆F508, G542X, N1303K, G551D, W1282X, 1717-1G→A, R553X, 621ϩ1G→T, R1162X, R117H, ∆I507, 1898ϩ1G→A, G85E, R347P, A455E, R560T, R334W, 3849ϩ10kbC→T, 3659delC, 1078delT, 2789ϩ5G→A, 711ϩ1G→T, 2184delA, 3120ϩ1G→A and I148T.
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ABCC7 p.Asn1303Lys 12151438:35:225
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86 CFTR mutations in 92 men with congenital bilateral absence of vas deferens Mutations CFTR mutation panels CF25 CF25 ϩ 5T ACMG25 ACMG25 ϩ 5T CF100 Mutations detected in ∆F508 39 39 39 39 39 CF25 mutation panel R117H 4 4 4 4 4 W1282X 4 4 4 4 4 G551D 3 3 3 3 3 G542X 1 1 1 1 1 N1303K 1 1 1 1 1 IVS8-polyT IVS8-5T 33 33 33 Additional mutations L206W 3 detected not in CF25 D1270N 2 mutation panel 1154InsTC 1 3272-26A→G 1 A455E 1 1 1 R334W 1 1 1 Q890X 1 Total 14 52 85 54 87 95 respectively, in the total number of patients with at least one mutation.
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ABCC7 p.Asn1303Lys 12151438:86:293
status: NEW
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91 CFTR genotypes in 92 men with congenital bilateral absence of vas deferens Genotypesa CFTR mutation panelsb CF25 CF25 ϩ 5T ACMG25 ACMG25 ϩ 5T CF100 Two mutations ∆F508/5T 16 16 16 W1282X/5T 4 4 4 ∆F508/R117Hc 3 3 3 3 3 G542X/5T 1 1 1 G551D/5T 1 1 1 ∆F508/L206W 2 ∆F508/A455E 1 1 1 ∆F508/3272-26A→G 1 Q890X/5T 1 L206W/5T 1 D1270N/D1270N 1 5T/5T 1 1 1 Sub-total 3 26 4 27 33 One mutation ∆F508/ϩ 36 20 35 19 16 5T/ϩ 9 9 7 G551D/ϩ 3 2 3 2 2 G542X/ϩ 1 1 R117H/ϩ 1 1 1 1 1 N1303K/ϩ 1 1 1 1 1 W1282X/ϩ 4 4 R334W/ϩ 1 1 1 1154InsTC/ϩ 1 Sub-total 46 33 46 33 29 Total (%) 49 (53.3) 59 (64.1) 50 (54.3) 60 (65.2) 62 (67.4) No mutation (%) 43 (46.7) 33 (35.9) 42 (45.7) 32 (34.8) 30 (32.6) aMutations L206W, 3272-26A→G, Q890X, D1270N, 1154InsTC and 5T are not in either CF25 and ACMG25 panels, while A455E and R334W are not in CF25, but are part of ACMG25 panel.
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ABCC7 p.Asn1303Lys 12151438:91:559
status: NEW
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PMID: 12200467 [PubMed] Vrettou C et al: "Multiplex sequence variation detection throughout the CFTR gene appropriate for preimplantation genetic diagnosis in populations with heterogeneity of cystic fibrosis mutations."
No. Sentence Comment
24 cells PCR ADO/total polymorphism (length bp) amplified product (%) cells (%) Patient 1 F508del 25 (196) 10 50 47 (94.0) 0/47 (0) 621 ϩ 1G→T 23 (192) 4 48 (96.0) 1/48 (2.1) Patient 2 N1303K 25 (196) 21 85 80 (94.1) 3/80 (3.8) 2789 ϩ 5G→A 18 (182) 14b 85 (100) 2/85 (2.4) Patient 3 E822X 17 (180) 13 part b 80 72 (90.0) 1/72 (1.4) F1052V 18 (182) 17b 75 (93.8) 2/75 (2.6) Heterozygotea 1719-9T→C 17 (180) 11 75 75 (100.0) 0/75 (0) R668C 13 part a Normal allele 18 (182) 74 (98.7) 1/74 (1.4) Microsatellite 290 268 (92.4) 29/268 (10.8) IVS8CA aIndividual heterozygote for D565G mutation in exon 12 (not included in assay) had two polymorphisms in cis to D565G (1719-9T→C in exon 11 and R668C in exon 13 part a), which were also in cis with 17 CA repeats in IVS8.
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ABCC7 p.Asn1303Lys 12200467:24:195
status: NEW
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PMID: 12215837 [PubMed] Scotet V et al: "Spatial and temporal distribution of cystic fibrosis and of its mutations in Brittany, France: a retrospective study from 1960."
No. Sentence Comment
118 His genotype was ∆F508/∆F508 Mutation Exon Basse-Bretagne Haute-Bretagne Brittanya ∆F508 10 446 75.6% 224 73.7% 672 75.0% 1078delT 7 31 5.3% 3 1.0% 34 3.8% G551D 11 21 3.6% 12 3.9% 33 3.7% N1303K 21 3 0.5% 9 3.0% 12 1.3% W846X 14a 9 1.5% 1 0.3% 10 1.1% 2789+5G→A 14b 3 0.5% 6 2.0% 9 1.0% 1717-1G→A 11 5 0.8% 3 1.0% 8 0.9% Y1092X 17b 1 0.2% 6 2.0% 7 0.8% 4005+1G→A 20 6 1.0% 1 0.3% 7 0.8% E60X 3 3 0.5% 3 1.0% 6 0.7% 621+1G→T 4 3 0.5% 3 1.0% 6 0.7% R347H 7 6 1.0% 0 0.0% 6 0.7% S492F 10 2 0.3% 3 1.0% 5 0.6% G542X 11 4 0.7% 1 0.3% 5 0.6% 3272-26A→G 17b 2 0.3% 3 1.0% 5 0.6% R117H 4 3 0.5% 1 0.3% 4 0.4% G91R 3 3 0.5% 0 0.0% 3 0.3% ∆I507 10 1 0.2% 2 0.7% 3 0.3% R553X 11 3 0.5% 0 0.0% 3 0.3% W1282X 20 2 0.3% 1 0.3% 3 0.3% A72D 3 0 0.0% 2 0.7% 2 0.2% G85E 3 0 0.0% 2 0.7% 2 0.2% F311L 7 0 0.0% 2 0.7% 2 0.2% 1221delCT 7 2 0.3% 0 0.0% 2 0.2% R560K 11 0 0.0% 2 0.7% 2 0.2% 2622+1G→A 13 2 0.3% 0 0.0% 2 0.2% S945L 15 0 0.0% 2 0.7% 2 0.2% I1234V 19 2 0.3% 0 0.0% 2 0.2% G1249R 20 2 0.3% 0 0.0% 2 0.2% 3905insT 20 2 0.3% 0 0.0% 2 0.2% Unidentified - 3 0.5% 0 0.0% 3 0.3% Total - 590 65.7% 304 34.3% 896 100% IVS17bTA, IVS17bCA) of Irish, Scottish, English, Breton and Czech subjects who were carriers of this mutation, and showed that all these alleles carried a unique haplotype (16-7-17), testifying to the Celtic origin of this mutation (Cashman et al. 1995).
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ABCC7 p.Asn1303Lys 12215837:118:210
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164 The distribution and the frequency of some mutations observed in the east of Brittany are close to those observed at the national level (2789+5G→A, N1303K, ∆I507).
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ABCC7 p.Asn1303Lys 12215837:164:155
status: NEW
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PMID: 12357328 [PubMed] McCormick J et al: "Demographics of the UK cystic fibrosis population: implications for neonatal screening."
No. Sentence Comment
79 It is envisaged that the proposed screening programme will be based on a three-stage protocol.6 In Table 3 Genotypes of the UK CF Caucasian and ISC populations Percentage of Percentage of genotyped UK CF genotyped UK CF Caucasian population ISC population Genotype n=4753 (%) n=78 (%) DF508/DF508 57.5 24.7 DF508/Unknown 11.5 3.5 DF508/G551D 5.1 0.0 DF508/G542X 2.8 0.0 Unknown/Unknown 2.7 27.1 DF508/621+1G?T 2.0 1.2 DF508/R117H 2.0 0.0 DF508/1898+1G?A 1.0 0.0 DF508/1717-G?A 0.9 0.0 DF508/N1303K 0.8 0.0 DF508 DI507 0.8 0.0 DF508/R553X 0.6 0.0 DF508/R560T 0.6 0.0 DF508/Q493X 0.5 0.0 G551D/Unknown 0.4 0.0 Other/Other 2.8 15.3* DF508/Other 6.7 0.0 Y569D/Y569D 0.0 8.2 L218X/L218X 0.0 3.5 1161delC/1161delC 0.0 3.5 R709X/V456A 0.0 2.4 G542X/G542X 0.4 2.4 Other/Unknown 1.0 3.5 The shaded areas represent the commonest genotypes in the ISC population.
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ABCC7 p.Asn1303Lys 12357328:79:491
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85 Table 4 The commonest CFTR mutations in the UK Genotypes UK CF population Genotyped UK Caucasian CF Genotyped UK CF ISC (n=9866 chromosomes) population (n=9506 chromosomes) population (n=156 chromosomes) CFTR mutation gene frequency per 1000 genes gene frequency per 1000 genes gene frequency per 1000 genes DF508 741.0 752.0 294.9 G551D 33.7 34.3 12.8 G542X 18.5 18.4 25.6 R117H 12.5 12.7 0.0 621+1G?T 12.7 12.7 6.4 1717-1G?A 5.8 5.8 0.0 1898+1G?A 5.7 5.9 0.0 N1303K 5.6 5.4 0.0 DI507 4.8 5.0 0.0 R560T 4.2 4.3 0.0 R553X 3.3 3.4 0.0 1154insTC 3.2 3.3 0.0 Q493X 2.8 2.9 0.0 3659delC 2.8 2.9 0.0 E60X 2.4 2.4 0.0 W1282X 2.7 2.7 0.0 P67L 2.1 2.1 0.0 G85E 2.1 2.0 0.0 V520F 1.6 1.7 0.0 1078delT 1.3 1.4 0.0 Y569D 1.5 0.0 96.2 L218X 0.6 0.0 38.5 1161delC 0.7 0.1 38.5 R1162X 0.9 0.6 19.2 R709X 0.4 0.2 12.8 3849+10kbC?T 1.2 0.8 19.2 S549R* 0.6 0.0 0.0 *S549R mutations appear in the non-Caucasian but not the ISC subgroup.
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ABCC7 p.Asn1303Lys 12357328:85:461
status: NEW
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97 In North America, DF508 accounts for 71.2%, with G542X (2.4%), G551D (2.4%), W1282X (1.4%), N1303K (1.3%) and R553X (0.9%).8 Genotype frequencies in CF have previously been shown to fit a Hardy - Weinberg model in a smaller regional UK study.9 In the current study, we find that the genotype frequencies only satisfy the Hardy-Weinberg equilibrium provided we exclude those without an identified CFTR mutation in the Other/Other category.
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ABCC7 p.Asn1303Lys 12357328:97:92
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101 When compared with a European CFTR geographic distribution,10 the UK CF patients possess a greater proportion of DF508, G551D and 621+1G?T mutations, and a smaller proportion of G542X, N1303K, W1282X and R1162X mutations.
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ABCC7 p.Asn1303Lys 12357328:101:185
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102 In France, the five most common genotypes were DF508/DF508 (47.8%), DF508 /G542X (3.4%), DF508/N1303K (2.7%), DF508 /1717-1G?A (2.1%) and DF508/2789+5G?A (1.5%) (Desgeorges M, personal communication) which is different to the commonest genotypes found in the UK population (Table 3).
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ABCC7 p.Asn1303Lys 12357328:102:95
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103 N1303K and G542X occur at a frequency of around 5% in Italy.11 In Germany, a study of 658 CF families revealed mutation frequencies of R553X (1.8%), N1303K (1.3%), G542X (1.1%), G551D (0.8%) and R347P (0.8%).12 The frequency of CFTR mutations recorded for just over 1000 patients for the Irish CF Database include G551D in 7%, R117H in 2% and DF508 in 72% of patients.13 In the white South African population, a paper based on 192 patients found that DF508 accounts for 76% of the mutations with 3272-26A?G (4%), 394delTT (3.6%) and G542X (1.3%) the other most common mutations.14 It is suggested that the 3272-26A?G and 394delTT mutations are more common due to a founder effect in white South Africans of European descent.
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ABCC7 p.Asn1303Lys 12357328:103:0
status: NEW
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ABCC7 p.Asn1303Lys 12357328:103:149
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PMID: 12359632 [PubMed] Zegarra-Moran O et al: "Correction of G551D-CFTR transport defect in epithelial monolayers by genistein but not by CPX or MPB-07."
No. Sentence Comment
70 The second mutation is presently unknown, but is not one of the 15 most frequent mutations found in the CF patients of Northeast Italy, namely F508del, I507del, R1162X, 2183AA4G, N1303K, 3849+10KbC4T, G542X, 1717-1G4A, R553X, Q552X, G85E, 711+5G4A, 3132delTG, 2789+5G4A, W1282X.
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ABCC7 p.Asn1303Lys 12359632:70:179
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PMID: 12394343 [PubMed] Rohlfs EM et al: "The I148T CFTR allele occurs on multiple haplotypes: a complex allele is associated with cystic fibrosis."
No. Sentence Comment
58 Diagnostic testing of individuals affected with CF, or suspected of having CF, identified eight individuals who were compound heterozygous for a severe mutation (⌬F508, N1303K, or Q890X) and I148T (Table 2).
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ABCC7 p.Asn1303Lys 12394343:58:176
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77 Table 2 3199del6 analysis in patients with a known or suspected diagnosis of CF and compound heterozygous for I148T and a severe CF mutation Indiv no. Indication for testing Ethnicity Age (yr) Mutation 1 Mutation 2 Intron 8 poly(T) 3199del6 17 Suspected CF NEC 4 ⌬F508 I148T 9, 9 pos 18 Suspected CF Caucasian, N. American 1 ⌬F508 I148T 9, 9 pos 19 Affected CF NEC Ͻ1 N1303K I148T 9, 9 pos 20 Suspected CF NEC 5 ⌬F508 I148T 9, 9 nega 22 Affected CF NEC 14 ⌬F508 I148T 9, 9 pos 39 Pancreatic steatorrhea NEC 3 ⌬F508 I148T 9, 9 pos 41 Suspected CF Hispanic 10 Q890X I148T 7, 9 pos 42 Affected CF NEC 20 ⌬F508 I148T 9, 9 pos NEC, Northern European Caucasian.
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ABCC7 p.Asn1303Lys 12394343:77:388
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PMID: 12394352 [PubMed] Richards CS et al: "Standards and guidelines for CFTR mutation testing."
No. Sentence Comment
50 Depending upon the ethnic group, these mutation frequencies may be difficult to obtain (Table 1).5-7 CF 2.8.1 The most common mutations in the Ashkenazi Jewish population have been described.8-10 These include W1282X, ⌬F508, G542X, N1303K, and 3849 ϩ 10 kbCϾT.
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ABCC7 p.Asn1303Lys 12394352:50:239
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307 ⌬F508 R553X R1162X 2184delA 3120ϩ1GϾA ⌬I507 G542X G551D W1282X N1303K 621ϩ1GϾT R117H 1717-1GϾA A455E R560T G85E R334W R347P 711ϩ1GϾT 1898ϩ1GϾA 1078delT 3849ϩ10kbCϾT 2789ϩ5GϾA 3659delC I148T CF 3.3.2 Inclusion of the common R117H mutation in the test panel screens for CBAVD as well as for CF: The phenotypic consequences of the R117H mutation are modulated in cis by the 5/7/9T polypyrimidine tract in intron 8 such that R117H/7T is associated with CBAVD and R117H/5T is associated with CF.34 Moreover, the 5T allele is associated as a trans mutation in CBAVD.35 It is recommended that the 5/7/9T variant be excluded from the routine carrier screen but tested as a reflex for carriers shown to be heterozygous for the R117H mutation.
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ABCC7 p.Asn1303Lys 12394352:307:89
status: NEW
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PMID: 12414835 [PubMed] Reboul MP et al: "Splice mutation 1811+1.6kbA>G causes severe cystic fibrosis with pancreatic insufficiency: report of 11 compound heterozygous and two homozygous patients."
No. Sentence Comment
127 Genotype-phenotype data are available especially for common genotypes,2 but information remains scarce or lacking for genotypes of compound heterozygotes with a rare mutation and homozygotes for a rare mutation.3 Among rare CFTR gene mutations, 1811+1.6kbA>G is practically absent in CF patients from other parts of France, but it is not rare in patients genotyped in the south west of France, occurring in fourth place after F508del, G542X, and N1303K.
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ABCC7 p.Asn1303Lys 12414835:127:446
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140 RESULTS The results of genotyping the 13 CF patients carrying the mutation 1811+1.6kbA>G were: two homozygotes for 1811+1.6kbA>G/1811+1.6kbA>G and 11 compound heterozygotes for 1811+1.6kbA>G and for another CFTR mutation, that is, F508del (n=6), N1303K (n=2), G542X (n=1), 2183 AA>G (n=1), and W1063X (n=1).
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ABCC7 p.Asn1303Lys 12414835:140:246
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148 Key points • The splice mutation 1811+1.6kbA>G of the CFTR gene is the fourth most frequent mutation (after F508del, G542X, and N1303K) in CF patients from the south west of France.
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ABCC7 p.Asn1303Lys 12414835:148:135
status: NEW
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160 Some of them are always responsible for a unique phenotype that can be either CF-PI (for instance, the case of N1303K in class II, G551D in class III, and R1066C in class IV), or CF-PS (for instance, the case of G551S in class III) or CBVAD for D1152H (class IV).
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ABCC7 p.Asn1303Lys 12414835:160:111
status: NEW
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PMID: 12437773 [PubMed] Huber K et al: "Survey of CF mutations in the clinical laboratory."
No. Sentence Comment
36 F508C, I507V, I506V polymorphism exon 11 1717-1G → A, G542X, S549N, G551D, R553X, R560T exon 20 W1282X exon 21 N1303K intron 19 3849+10kb C → T Innogenetics assay: exon 3 394delTT, G85E, E60X exon/intron 4 621+1G-T, R117H exon 7 1078delT, R347P, R334W exon 13 2143delT, 2183AA-G, 2184delA exon 19 R1162X, 3659delC intron 5 711+5G-A intron8/exon 9 A455E,, 5T,7T,9T intron 14b 2789+5G-A intron 19 3849+10kb C-T Table 2: Genotypes of patients with mutations, final results Group 1) (patients with symptoms typical for/indicative of CF) No.
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ABCC7 p.Asn1303Lys 12437773:36:118
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PMID: 12439892 [PubMed] Kilinc MO et al: "Highest heterogeneity for cystic fibrosis: 36 mutations account for 75% of all CF chromosomes in Turkish patients."
No. Sentence Comment
80 Haplotypes Associated With the Mutations Identified in 83 Turkish CF Patients* Mutation Total number of alleles Number of alleles Number of patients Haplotypes Homo Hetero DF508 39 (23.5) 6 7 23 M 28 13 1 0 1 6 7 23 M 30 13 1 0 1 6 9 23 M 31 13 1 0 1 6 7 23 M 31 13 11 4 3 6 7 23 M 7 17 2 0 2 6 7 16 M 31 13 3 1 1 6 7 17 M 31 13 17 5 7 6 7 17 M 32 13 3 1 1 1677delTA 12 (7.2) 7 7 16 V 30 13 12 5 2 2183AA > G 7 (4.2) 7 7 16 M 30 13 1 0 1 7 9 16 M 31 13 4 2 0 7 7 16 M 32 13 2 1 0 G542X 6 (3.6) 6 7 23 M 32 13 6 3 0 F1052V 5 (3.0) 6 7 17 M 7 13 4 1 2 7 5 17 M 7 17 1 0 1 W1282X 5 (3.0) 7 7 17 M 7 17 4 1 2 7 7 17 M 7 18 1 0 1 E92K 4 (2.4) 7 7 16 V 46 13 3 1 1 7 7 17 V 46 13 1 0 1 1525 À 1G > A 4 (2.4) 7 7 17 M 7 17 4 2 0 2789 þ 5G > A 4 (2.4) 7 9 17 M 7 17 3 1 1 7 5 17 M 7 17 1 0 1 N1303K 4 (2.4) 7 7 23 M 31 13 2 0 2 6 7 22 M 30 13 1 0 1 6 7 23 M 30 13 1 0 1 A46D 3 (1.8) 6 9 23 M 31 13 1 0 1 6 7 23 M 31 13 2 1 0 2184insA 3 (1.8) 7 5 17 V 30 13 1 0 1 7 7 16 V 30 13 2 0 2 R1070Q 3 (1.8) 7 7 16 M 31 13 1 0 1 7 7 17 M 31 13 2 0 2 Q493Pa 2 (1.2) 6/7 5 16 M 46 13 2 1 0 3849 þ 5G > Aa 2 (1.2) 7 7 16 M 31 13 2 1 0 CFTRdele17b,18a 2 (1.2) 6 9 16 V - - 2 1 0 K68Ea 1 (0.6) 6 9 17 M 7 13 1 0 1 R74W 1 (0.6) 6 7 16 M 32 16 1 0 1 306delTAGA 1 (0.6) 7 7 16 M 7 17 1 0 1 D110H 1 (0.6) 7 9 16 V 30 13 1 0 1 I125T 1 (0.6) 6 7 23 V 7 16 1 0 1 406 À 3T > Ca 1 (0.6) 7 7 16 V 33 17 1 0 1 I148T 1 (0.6) 6/7 7 16/17 M 7 17/23 1 0 1 621 þ 1G > T 1 (0.6) 6 7 21 V 31 13 1 0 1 R347P 1 (0.6) 7 9 17 V 30 13 1 0 1 S466X 1 (0.6) 7 7 23 M 33 13 1 0 1 L571S 1 (0.6) 7 7 16 V 29 13 1 0 1 1717 À 1G > A 1 (0.6) 7 9 17 M 7 16 1 0 1 E608Ga 1 (0.6) 7 9 16 M/V 29/31 13 1 0 1 2043delG 1 (0.6) 7 9 17 M 7 17 1 0 1 P1013L 1 (0.6) 6 5 16 M 21 18 1 0 1 R1066L 1 (0.6) 7 7 17 M 7 13 1 0 1 3129del4 1 (0.6) 7 7 16 V 29 13 1 0 1 V1147Ia 1 (0.6) 6 7 17 M 33 17 1 0 1 S1235R 1 (0.6) 6 7 17 M 39 13 1 0 1 CFTRdele2,3 1 (0.6) 7 7 16 V 33 13 1 0 1 Total 125 (75) 125 32 61 *The order of the polymorphisms is IVS6GATT, Tn, IVS8CA, M470V, IVS17BTA and IVS17BCA.
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ABCC7 p.Asn1303Lys 12439892:80:794
status: NEW
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PMID: 12483292 [PubMed] Mekus F et al: "Genes in the vicinity of CFTR modulate the cystic fibrosis phenotype in highly concordant or discordant F508del homozygous sib pairs."
No. Sentence Comment
11 The frequent CFTR mutations, F508del, N1303K, and G542X, are associated with several intragenic STRP haplotypes, but occur on the same flanking SNP haplotype (Dörk et al. 1992; Sereth et al. 1993; Morral et al. 1993; Cuppens et al. 1994; Morral et al. 1996).
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ABCC7 p.Asn1303Lys 12483292:11:38
status: NEW
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PMID: 12503104 [PubMed] Kulczycki LL et al: "A clinical perspective of cystic fibrosis and new genetic findings: relationship of CFTR mutations to genotype-phenotype manifestations."
No. Sentence Comment
84 At the age of 60, genetic testing indicated two mutations H1282X (severe) and A 445E (mild), confirming the CF diagnosis as a compound heterzygote with normal alleles for D F508, -G551D, -R553X, -G542X, and N1303K [Kulczycki et al., 1998].
X
ABCC7 p.Asn1303Lys 12503104:84:207
status: NEW
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PMID: 12509709 [PubMed] Watson MS et al: "Cystic fibrosis carrier screening: issues in implementation."
No. Sentence Comment
58 Among five individuals with CF and with ⌬F508 or N1303K mutation and I148T, four had I148T on a background of 9T and 3199del6.
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ABCC7 p.Asn1303Lys 12509709:58:56
status: NEW
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PMID: 12521276 [PubMed] Eskandarani HA et al: "Cystic fibrosis transmembrane regulator gene mutations in Bahrain."
No. Sentence Comment
25 Isolation and PCR amplification of genomic DNA Genomic DNA was extracted from leucocytes according to standard procedures.10 PCR amplification of DNA was performed by preparation of a 50-µl reaction mixture that contained appropriate primers using standard protocols.4 Mutation analysis All patients were screened for 15 common mutations amongst Arabs by restriction enzyme digestion analysis with appropriate enzymes according to specific protocols4,5 and/or using the amplification refractory mutation system (ARMS-PCR) technique.11 These mutations were: 406-2A→G (intron 3), 425del42 (exon 4), 475G→T (exon 4), 548A→T (exon 4), 1161delC (exon 7), 1548delG (exon10), F508 (exon 10), G542X (exon 11), 2043delG (exon 13), 3120+1G→A (intron 16), 3661A→T (exon 19), 3849+10KbC→T (intron 19), I1234V (exon 19), W1282X (exon 20), and N1303K (exon 21).
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ABCC7 p.Asn1303Lys 12521276:25:877
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PMID: 12544470 [PubMed] Strom CM et al: "Extensive sequencing of the cystic fibrosis transmembrane regulator gene: assay validation and unexpected benefits of developing a comprehensive test."
No. Sentence Comment
54 Table 2 Mutant samples used for validation of sequencing assay Mutation expected wt/wt (3 patients) delta F508/wt (2 patients) R117H/wt (3 patients) 2789 ϩ 5 G 3 A/2789 ϩ 5 G 3 A (both parents confirmed carriers) R117H/delta F508 (2 patients) delta F508/I148T delta F508/R1066C delta F508/3848 ϩ 10 kb C 3 T delta F508/G542X R117H/I148T (2 patients) 2307 delA/N1303K deltaF 508/711 ϩ 1 G 3 T deltaF 508/1898 ϩ 1 G 3 A G551D/N1303K 2789 ϩ 5G3A.
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ABCC7 p.Asn1303Lys 12544470:54:378
status: NEW
X
ABCC7 p.Asn1303Lys 12544470:54:454
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PMID: 12630958 [PubMed] Devaney J et al: "Cystic fibrosis mutation frequencies in an Irish population."
No. Sentence Comment
18 In a selected cohort of 40 patients, six other common ABCC7 mutations were screened for, using PCR-REA: R347P, A455E, R1162X, 3849‡10kbC> T, W1282X and N1303K.
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ABCC7 p.Asn1303Lys 12630958:18:157
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27 Samples (n ˆ 40) were screened using an in-house optimized protocol to screen for six additional mutations (R347P, A455E, R1162X, 3849 ‡ 10kbC > T, W1282X and N1303K).
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ABCC7 p.Asn1303Lys 12630958:27:169
status: NEW
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PMID: 12651880 [PubMed] Witt H et al: "Chronic pancreatitis and cystic fibrosis."
No. Sentence Comment
430 Nucleus Class I defective protein synthesis (R553X, W1282X, 3950delT) Class II abnormal processing/trafficking (del508, N1303K) Class VI defective regulation of other ion channels (del508, G551D) Class V reduced synthesis (3849+10kbC>T) Class IV decreased conductance (R117H, R347P, D1152H) Class III defective activation (G551D) I II VI V III IV RD ATP Endoplasmic reticulum NBD NBD Golgi mutations result in a decreased amount of functional protein by abnormal splicing or reduced trafficking.
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ABCC7 p.Asn1303Lys 12651880:430:120
status: NEW
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PMID: 12658038 [PubMed] Walkowiak J et al: "Longitudinal follow-up of exocrine pancreatic function in pancreatic sufficient cystic fibrosis patients using the fecal elastase-1 test."
No. Sentence Comment
51 RESULTS Among the patients studied, the following mutations of the CFTR gene were present (n): ⌬F508 (223), 621+G-T (10), N1303K (9), 3849+10kbC-T (6), G542X (5), CFTRdele2,3(21kB) (4), E822X (4), 1717-1G-A (3), E836X (3), G1069-L88X (2), R533X (1), G85E (1), 1677delTA (1), G1069R (1), 1525-1G-A (1), and 2789+5G-A (1).
X
ABCC7 p.Asn1303Lys 12658038:51:129
status: NEW
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PMID: 12680831 [PubMed] Cimmino M et al: "Clinical characteristics and genotype analysis of patients with cystic fibrosis and nasal polyposis."
No. Sentence Comment
47 Analysis of mutations in the CFTR gene as tested by the multiplex polymerase chain reaction (PCR), followed by the reverse dot-blot technique, which searches for 29 of the most frequent mutations (DF508, N1303K, G542X, W1282X, 1717±1 G-A, R553X, 2183 AA-G, DI507, G551D, R560T, 3849 ‡ 10kbC > T, R1162X, 3659delC, 3905insT, G85E, 621 ‡ 1GT, R117H, R347P, R334W, A455E, 2789 ‡ 5GA, Q552X, S1251N, 3905insT, 394delTT, E60X, 2143delT, 2184delA, 711 ‡ 5G > A), and by ASO dot-blot for the following mutations: I148T, R1158X, 4016 ‡ 1T, G1244E G >A.26 Statistical analysis was performed using multivariate analysis, by forward stepwise comparison; it was done to ®nd out which of the examined characteristics could be associated (P < 0.01) to nasal polyposis.
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ABCC7 p.Asn1303Lys 12680831:47:204
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91 Frequency (percentage) of compound heterozygous genotypes by nasal polyposis status in patients with cystic fibrosis Group with nasal polyposis (n ˆ 15) Comparison group (n ˆ 20) DF508/G542X 2 (13.33) 2 (10) DF508/N1303K 2 (13.33) 4 (20) DF508/AA2183G 1 (6.67) 0 DF508/IG1717 1 (6.67) 1 (5) DF508/W1282X 1 (6.67) 1 (5) DF508/unspecified 8 (53.33) 12 (60) their study group included patients with nasal polyposis that required surgery.
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ABCC7 p.Asn1303Lys 12680831:91:224
status: NEW
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PMID: 12734544 [PubMed] Lao O et al: "Spatial patterns of cystic fibrosis mutation spectra in European populations."
No. Sentence Comment
66 The correlations with Y-chromosome-based Table 1 94 middle Eastern, North African and European populations used in the analysis Population 2N F508del G542X G551D N1303K W1282X Rare Other Unknown Hmax Ymax Incidence Referencesa Austria 592 0.660 0.022 0.012 0.005 0.002 0.064 0.019 0.216 0.562 0.96 49 Belgium 646 0.752 0.025 0.002 0.028 0.012 0.053 0.046 0.082 0.430 0.56 50 Bulgaria 208 0.654 0.034 0.000 0.067 0.000 0.096 0.067 0.082 0.563 0.97 51 Crete 26 0.462 0.077 0.000 0.038 0.000 0.231 0.038 0.154 0.785 2.87 Czech Republic 584 0.697 0.021 0.034 0.026 0.005 0.051 0.021 0.146 0.512 0.78 Denmark 678 0.872 0.006 0.001 0.010 0.001 0.034 0.035 0.040 0.239 0.23 0.000210 Great Britain 0.000414b North England 4111 0.772 0.008 0.023 0.005 0.001 0.032 0.011 0.148 0.403 0.50 Scotland 1167 0.751 0.033 0.061 0.003 0.003 0.033 0.023 0.093 0.430 0.56 0.000504 South England 3679 0.769 0.020 0.029 0.005 0.002 0.032 0.009 0.133 0.407 0.51 Wales 372 0.659 0.024 0.030 0.005 0.000 0.134 0.065 0.083 0.557 0.94 Estonia 25 0.640 0.000 0.000 0.000 0.000 0.160 0.080 0.120 0.577 1.02 Former Yugoslavia 203 0.700 0.030 0.000 0.010 0.005 0.039 0.069 0.148 0.506 0.76 Finland 52 0.462 0.019 0.000 0.000 0.000 0.288 0.019 0.212 0.713 1.90 France 0.000232 Alsace 126 0.595 0.024 0.000 0.016 0.008 0.040 0.008 0.310 0.646 1.38 Aquitaine 116 0.612 0.034 0.000 0.017 0.000 0.043 0.009 0.284 0.626 1.26 Auvergne 102 0.725 0.039 0.000 0.029 0.010 0.020 0.000 0.176 0.474 0.67 Burgundy 168 0.702 0.024 0.000 0.006 0.000 0.060 0.006 0.202 0.507 0.77 Brittany 582 0.744 0.009 0.024 0.017 0.003 0.064 0.002 0.137 0.444 0.60 0.000343 Centre 218 0.716 0.050 0.000 0.023 0.000 0.023 0.000 0.188 0.486 0.71 Champagne 182 0.665 0.049 0.000 0.016 0.000 0.055 0.005 0.209 0.556 0.94 Franche-Comt ´ e 118 0.746 0.085 0.000 0.085 0.025 0.059 0.000 0.000 0.431 0.56 Languedoc 90 0.700 0.022 0.011 0.033 0.000 0.044 0.000 0.189 0.511 0.78 Llimousin 44 0.545 0.023 0.000 0.068 0.000 0.023 0.023 0.318 0.705 1.83 Loire Valley 308 0.737 0.006 0.019 0.013 0.003 0.032 0.000 0.188 0.457 0.63 Lorraine 286 0.717 0.031 0.000 0.000 0.000 0.042 0.000 0.210 0.486 0.70 Lower Normandie 174 0.644 0.017 0.023 0.017 0.000 0.069 0.000 0.230 0.585 1.06 Midi-Pyr ´ en ´ ees 114 0.649 0.035 0.000 0.018 0.009 0.018 0.000 0.272 0.580 1.03 Nord 468 0.660 0.019 0.004 0.015 0.002 0.053 0.006 0.239 0.563 0.97 Paris Region 830 0.643 0.027 0.007 0.010 0.012 0.035 0.000 0.266 0.585 1.06 Picardie 200 0.650 0.040 0.000 0.040 0.010 0.080 0.000 0.180 0.574 1.01 Poitou 100 0.770 0.030 0.000 0.020 0.000 0.020 0.000 0.160 0.408 0.51 Provence- Cote d`Azur 178 0.674 0.028 0.000 0.051 0.017 0.028 0.006 0.197 0.544 0.89 Rhone-Alpes 668 0.668 0.036 0.001 0.027 0.009 0.018 0.009 0.232 0.552 0.92 Upper Normandie 248 0.645 0.020 0.008 0.012 0.004 0.048 0.004 0.258 0.584 1.05 Germany Baden-W ¨ urttemberg 59 0.763 0.000 0.000 0.034 0.000 0.051 0.102 0.051 0.412 0.52 Bavaria 177 0.740 0.017 0.017 0.000 0.000 0.040 0.011 0.175 0.453 0.62 Berlinc 132 0.773 0.015 0.000 0.023 0.000 0.038 0.015 0.136 0.403 0.50 Bremend 74 0.689 0.014 0.014 0.000 0.000 0.054 0.014 0.216 0.528 0.84 Lower Saxony 198 0.803 0.005 0.005 0.015 0.000 0.015 0.030 0.126 0.355 0.41 North-Rhine/ Westphalia 174 0.736 0.006 0.006 0.000 0.006 0.069 0.034 0.144 0.458 0.63 Saxonye 83 0.639 0.012 0.012 0.024 0.000 0.036 0.036 0.241 0.594 1.10 Rhineland-Palatinaf 59 0.525 0.017 0.000 0.051 0.000 0.085 0.068 0.254 0.721 1.99 Greece Ipiros/Ionian Islands 46 0.609 0.000 0.000 0.043 0.000 0.087 0.043 0.217 0.632 1.30 Peloponese/Attica 89 0.573 0.000 0.022 0.045 0.000 0.146 0.045 0.169 0.667 1.52 Thesalia/Macedonia/ Thrace 61 0.672 0.066 0.000 0.033 0.000 0.033 0.082 0.115 0.543 0.89 Hungary 57 0.439 0.018 0.000 0.018 0.018 0.070 0.018 0.421 0.811 3.43 Italy Abruzzo 66 0.500 0.061 0.000 0.091 0.076 0.030 0.000 0.242 0.739 2.19 Basilicata 75 0.467 0.107 0.000 0.067 0.027 0.067 0.013 0.253 0.769 2.61 Calabria 149 0.430 0.034 0.000 0.047 0.020 0.054 0.034 0.383 0.813 3.46 distances were similar (r ¼ 0.147, P ¼ 0.116 and after controlling for geographical distance r ¼ 0.054, P ¼ 0.296).
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ABCC7 p.Asn1303Lys 12734544:66:163
status: NEW
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68 Table 1 (continued) Population 2N F508del G542X G551D N1303K W1282X Rare Other Unknown Hmax Ymax Incidence Referencesa Campania 223 0.610 0.040 0.000 0.067 0.018 0.040 0.004 0.220 0.623 1.25 Emilia-Romagna 242 0.541 0.058 0.000 0.025 0.008 0.050 0.000 0.318 0.704 1.82 0.000170 Friuli 24 0.375 0.125 0.000 0.042 0.042 0.083 0.083 0.250 0.855 4.85 Lazio 236 0.462 0.030 0.000 0.093 0.013 0.034 0.013 0.356 0.778 2.75 Liguria 44 0.591 0.114 0.000 0.023 0.000 0.045 0.000 0.227 0.646 1.38 Lombardia 399 0.499 0.038 0.000 0.038 0.010 0.090 0.050 0.276 0.743 2.24 Marche 144 0.389 0.056 0.000 0.083 0.014 0.063 0.007 0.389 0.841 4.29 Molise 27 0.481 0.037 0.000 0.074 0.000 0.037 0.000 0.370 0.775 2.70 Piemonte 117 0.675 0.034 0.000 0.000 0.000 0.043 0.017 0.231 0.544 0.89 Puglia 245 0.543 0.053 0.000 0.073 0.000 0.041 0.012 0.278 0.698 1.77 Sardegna 141 0.582 0.057 0.000 0.028 0.000 0.028 0.142 0.163 0.641 1.35 Sicilia 387 0.525 0.062 0.000 0.034 0.023 0.067 0.021 0.269 0.719 1.97 Toscana 191 0.508 0.042 0.000 0.037 0.010 0.031 0.005 0.366 0.740 2.21 Trentino 113 0.513 0.027 0.009 0.009 0.009 0.204 0.053 0.177 0.718 1.96 Umbria 37 0.676 0.081 0.000 0.027 0.000 0.027 0.000 0.189 0.545 0.90 Veneto 552 0.449 0.014 0.000 0.031 0.000 0.188 0.033 0.284 0.785 2.87 0.000370 Ireland Republic of Ireland 509 0.727 0.010 0.069 0.004 0.000 0.037 0.014 0.139 0.467 0.65 0.000684 Northern Ireland 876 0.619 0.021 0.045 0.001 0.000 0.063 0.047 0.205 0.612 1.19 0.000553 52 Israel 367 0.322 0.054 0.000 0.030 0.362 0.065 0.082 0.084 0.754 2.39 0.000304 Lebanon 40 0.350 0.000 0.000 0.100 0.200 0.025 0.225 0.100 0.794 3.04 0.000390 53 Netherlands 1442 0.744 0.013 0.001 0.009 0.007 0.072 0.019 0.135 0.444 0.60 0.000252 Norway 168 0.667 0.006 0.012 0.006 0.000 0.071 0.000 0.238 0.555 0.93 0.000152 Poland 444 0.662 0.023 0.007 0.020 0.002 0.043 0.020 0.223 0.560 0.96 Portugal Faro/Beja 25 0.680 0.000 0.000 0.000 0.000 0.040 0.000 0.280 0.547 0.90 Lisboag 100 0.480 0.030 0.000 0.000 0.000 0.080 0.060 0.350 0.767 2.57 Setubal/Evora 33 0.485 0.000 0.000 0.000 0.000 0.121 0.091 0.303 0.767 2.57 Russia 445 0.618 0.007 0.002 0.004 0.004 0.031 0.031 0.301 0.617 1.22 0.000051 Slovakia 254 0.559 0.075 0.000 0.035 0.016 0.075 0.016 0.224 0.680 1.62 Spain Andalucı´a 314 0.538 0.086 0.013 0.013 0.013 0.083 0.096 0.159 0.694 1.73 Arago´n 65 0.523 0.031 0.000 0.015 0.000 0.123 0.138 0.169 0.708 1.86 Castilla la Mancha 69 0.478 0.058 0.000 0.043 0.000 0.014 0.029 0.377 0.771 2.63 Paı´s Valencia` 125 0.464 0.104 0.000 0.056 0.000 0.096 0.040 0.240 0.771 2.63 Castilla Leo´n/ La Rioja 187 0.604 0.048 0.000 0.011 0.000 0.102 0.107 0.128 0.623 1.24 54 Catalonia 109 0.642 0.055 0.000 0.037 0.009 0.083 0.064 0.110 0.582 1.05 0.000187 Extremadura 63 0.460 0.048 0.000 0.016 0.000 0.079 0.127 0.270 0.776 2.72 Galicia 93 0.624 0.097 0.000 0.011 0.000 0.161 0.075 0.032 0.596 1.11 Madrid 51 0.510 0.059 0.020 0.039 0.000 0.059 0.020 0.294 0.742 2.23 Murcia 40 0.250 0.125 0.000 0.025 0.025 0.175 0.200 0.200 0.889 6.74 Basque Country 31 0.710 0.000 0.000 0.000 0.000 0.065 0.097 0.129 0.497 0.74 Sweden 165 0.733 0.006 0.000 0.000 0.000 0.103 0.085 0.073 0.448 0.60 0.000130 Switzerland 95 0.432 0.032 0.000 0.011 0.000 0.263 0.168 0.095 0.732 2.11 Tunisia 78 0.179 0.090 0.000 0.064 0.026 0.128 0.115 0.397 0.941 14.51 55 Turkey 263 0.274 0.038 0.000 0.042 0.004 0.087 0.114 0.441 0.907 8.44 56 Ukraine 396 0.543 0.000 0.005 0.000 0.000 0.018 0.000 0.434 0.706 1.84 57 Total 29131 0.674 0.025 0.015 0.017 0.009 0.053 0.024 0.182 0.586 1.06 N, sample size (in number of CF chromosomes); F508del, G542X, G551D, 1303K, and W1282X, relative frequencies of the main mutations; rare, relative frequency of mutations not listed in Table 2 of reference 58; other, relative frequency of mutations listed in Table 2 of reference 58. unknown, fraction of chromosomes asociated to disease bearing unidentified mutations.
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ABCC7 p.Asn1303Lys 12734544:68:54
status: NEW
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PMID: 12794695 [PubMed] Timmreck LS et al: "Analysis of cystic fibrosis transmembrane conductance regulator gene mutations in patients with congenital absence of the uterus and vagina."
No. Sentence Comment
82 CFTR Gene Mutations Tested DF508 R334W Y1092X 5T variant Y122X R347H G542X S549R 3,849 þ 4 G551D 3,849 þ 10 kb 2,789 þ 5 W1282X R553X 711 þ 1 3,905 þ T 621 þ 1 1,898 þ 1 N1303K 1,717À1 R1162X R117H 1078dT A455E D1507 Q493X 218dA R347P V520F G85E R560T S549N 3659dC Wolffian duct must occur at a time when the Mu¨llerian duct is no longer dependent on the Wolffian duct for development.
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ABCC7 p.Asn1303Lys 12794695:82:205
status: NEW
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PMID: 12815607 [PubMed] Scotet V et al: "Comparison of the CFTR mutation spectrum in three cohorts of patients of Celtic origin from Brittany (France) and Ireland."
No. Sentence Comment
7 In Brittany, the most common abnormalities were: c.1078delT (3.6%), c.4041C>G (N1303K: 1.4%), c.2670G>A (W846X2: 1.0%) and c.1717-1G>A (1.0%), whereas in the cohort of Dublin, the main mutations were: c.482G>A (R117H: 3.0%), c.1811G>C (R560T: 2.4%) and c.621+1G>T (1.7%).
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ABCC7 p.Asn1303Lys 12815607:7:79
status: NEW
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19 This spectrum is noteworthy because it includes a main mutation, accounting for 70% of the mutated alleles world-wide (the deletion F508del), four other mutations observed with a frequency over 1% (G542X: 2.4%, G551D: 1.6%, N1303K: 1.3%, W1282X: 1.2%) and a multitude of private abnormalities (Tsui, 2003).
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ABCC7 p.Asn1303Lys 12815607:19:224
status: NEW
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44 Firstly, the National Centre for Medical Genetics, Dublin performed an analysis of the most common CFTR mutations, using the ARMS test (Ferrie et al., 1992), which enables the detection of the following mutations: F508del, R117H, I507del, G542X, G551D, R560T, N1303K, R352Q, 1717-1G>A and 621+1G>T.
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ABCC7 p.Asn1303Lys 12815607:44:260
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50 Dublin Centre 1262 CF alleles 35 mutations F508del 76.5% G551D 6.5% R117H 3.0% R560T 2.4% 621+1G>T 1.7% Cork Area 278 CF alleles 10 mutations F508del 81.3% G551D 9.7% R117H 1.4% Brittany 778 CF alleles 62 mutations F508del 74.8% G551D 3.7% 1078delT 3.6% N1303K 1.4% W846X2 1.0% 1717-1G>A 1.0% Statistical analysis We determined the spectrum of the CFTR mutations identified in the three cohorts of patients and compared their respective frequencies by a Chi square test.
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ABCC7 p.Asn1303Lys 12815607:50:254
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64 Spectrum of the CFTR Mutations Identified in the Cohorts from Brittany, Dublin Centre, and Cork Area Nucleotide Amino acid change * change Exon Number Frequency Number Frequency Number Frequency 211delG 2 1 0.1% 310G>T E60X 3 5 0.6% 4 0.3% 347C>A A72D 3 1 0.1% 368G>A W79X 3 1 0.1% 386G>A G85E 3 2 0.3% 3 0.2% 403G>A G91R 3 2 0.3% 482G>A R117H 4 4 0.5% 38 3.0% 4 1.4% 498T>A Y122X 4 1 0.1% 574delA 4 1 0.1% 577G>A G149R 4 1 0.1% 621+1G>T int 4 5 0.6% 21 1.7% 790C>T Q220X 6a 1 0.1% 875+1G>C int 6a 1 0.4% 905delG 6b 1 0.1% 1065C>G F311L 7 2 0.3% 1078delT 7 28 3.6% 1132C>T R334W 7 1 0.1% 1172G>A R347H 7 5 0.6% 1172G>T R347L 7 1 0.1% 1172G>C R347P 7 1 0.1% 1187G>A R352Q 7 3 0.2% 2 0.7% 1208A>G Q359R 7 1 0.1% 1154insTC 7 2 0.2% 1221delCT 7 2 0.3% 1248+1G>A int 7 1 0.1% 1249-27delTA int 7 1 0.4% 1334G>A W401X 8 1 0.1% 1461ins4 9 5 0.4% 1471delA 9 2 0.2% 1607C>T S492F 10 2 0.3% 1609C>T Q493X 10 1 0.1% 1648_1653delATC I507del 10 3 0.4% 10 0.8% 1 0.4% 1652_1655del 3 bp F508del 10 582 74.8% 966 76.5% 226 81.3% 1690G>T V520F 10 4 0.3% 1717-1G>A int 10 8 1.0% 9 0.7% 1756G>T G542X 11 5 0.6% 8 0.6% 1779T>G S549R 11 1 0.1% 1784G>A G551D 11 29 3.7% 82 6.5% 27 9.7% 1789C>G R553G 11 1 0.1% 1789C>T R553X 11 3 0.4% 1 0.1% 1806delA 11 1 0.1% 1811G>A R560K 11 2 0.3% 1811G>C R560T 11 30 2.4% 2 0.7% 1819T>A Y563N 12 1 0.1% 1853C>A P574H 12 1 0.1% 1898+1G>A int 12 1 0.1% 2184delA 13 1 0.1% 1 0.1% 2184insA 13 1 0.1% 2622+1G>A int 13 1 0.1% 2 0.2% 2622+1G>T int 13 1 0.1% 2623-2A>G ** int 13 1 0.1% 2670G>A W846X2 14a 8 1.0% 2752-1G>T int 14a 1 0.1% 2752-26A>G int 14a 2 0.2% 2789+5G>A int 14b 6 0.8% 2966C>T S945L 15 2 0.3% 3007delG 15 4 0.3% 3040G>C G970R 15 1 0.1% 3062C>T S977F 16 1 0.1% 3120+1G>A int 16 1 0.1% 3272-26A>G int 17a 4 0.5% 2 0.2% 2 0.7% 3320dupli(CTATG) 17b 1 0.1% 3329G>A R1066H 17b 1 0.1% 3340C>T R1070W 17b 1 0.1% 3408C>A Y1092X 17b 7 0.9% 3442G>T E1104X 17b 1 0.1% 3446T>G ** M1105R 17b 1 0.1% 3586G>C D1152H 18 1 0.1% 3601-17T>C + 1367delC int 18 + 9 1 0.1% 3616C>T R1162X 19 1 0.1% 2 0.2% 3659delC 19 2 0.2% 3832A>G I1234V 19 2 0.3% 3849+4A>G int 19 1 0.1% 3849+10kbC>T int 19 3 0.2% 3877G>A G1249R 20 1 0.1% 3884G>A S1251N 20 1 0.1% 3898insC 20 1 0.1% 3905insT 20 2 0.3% 3978G>A W1282X 20 3 0.4% 4005+1G>A int 20 6 0.8% 4016insT 21 1 0.1% 4041C>G N1303K 21 11 1.4% 5 0.4% 4136T>C L1335P 22 1 0.1% 1 0.4% 4279insA 23 1 0.1% Unidentified Unidentified - 3 0.4% 41 3.2% 11 4.0% Total 778 100.0% 1262 100.0% 278 100.0% * All nucleotide changes correspond to cDNA numbering.
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ABCC7 p.Asn1303Lys 12815607:64:2266
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72 In Brittany, the four mutations found with a frequency above 1% were: 1078delT (3.6%), N1303K (1.4%), W846X2 (TGGàTGA) (1.0%) and 1717-1G>A (1.0%).
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ABCC7 p.Asn1303Lys 12815607:72:87
status: NEW
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76 Number Frequency Number Frequency 1652_1655del 3 bp F508del 384 75.6% 196 73.1% 582 74.8% 1784G>A G551D 17 3.3% 12 4.5% 29 3.7% 1078delT 25 4.9% 3 1.1% 28 3.6% 4041C>G N1303K 3 0.6% 8 3.0% 11 1.4% 2670G>A W846X2 7 1.4% 1 0.4% 8 1.0% 1717-1G>A 5 1.0% 3 1.1% 8 1.0% 3408C>A Y1092X 1 0.2% 6 2.2% 7 0.9% 2789+5G>A 2 0.4% 4 1.5% 6 0.8% 4005+1G>A 5 1.0% 1 0.4% 6 0.8% 310G>T E60X 3 0.6% 2 0.7% 5 0.6% 621+1G>T 2 0.4% 3 1.1% 5 0.6% 1172G>A R347H 5 1.0% 5 0.6% 1756G>T G542X 4 0.8% 1 0.4% 5 0.6% 482G>A R117H 3 0.6% 1 0.4% 4 0.5% 3272-26A>G 2 0.4% 2 0.7% 4 0.5% 1648_1653delATC I507del 1 0.2% 2 0.7% 3 0.4% 1789C>T R553X 3 0.6% 3 0.4% 3978G>A W1282X 2 0.4% 1 0.4% 3 0.4% Unidentified Unidentified 3 0.6% 3 0.4% Total Total 508 100.0% 268 100.0% 778 100.0% Basse-Bretagne Haute-Bretagne Brittany * Amino acid change Nucleotide change Table 3: Distribution of the Main CFTR Nutations Observed in the Irish Cohorts (Dublin and Cork) The 62 mutations detected in Brittany combined to give 81 different genotypes in CF patients.
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ABCC7 p.Asn1303Lys 12815607:76:168
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98 Number Frequency Number Frequency 1652_1655del 3 bp F508del 966 76.5% 226 81.3% 1192 77.4% 1784G>A G551D 82 6.5% 27 9.7% 109 7.1% 482G>A R117H 38 3.0% 4 1.4% 42 2.7% 1811G>C R560T 30 2.4% 2 0.7% 32 2.1% 621+1G>T 21 1.7% 21 1.4% 1648_1653delATC I507del 10 0.8% 1 0.4% 11 0.7% 1717-1G>A 9 0.7% 9 0.6% 1756G>T G542X 8 0.6% 8 0.5% 1187G>A R352Q 3 0.2% 2 0.7% 5 0.3% 1461ins4 5 0.4% 5 0.3% 4041C>G N1303K 5 0.4% 5 0.3% 310G>T E60X 4 0.3% 4 0.3% 1690G>T V520F 4 0.3% 4 0.3% 3007delG 4 0.3% 4 0.3% 3272-26A>G 2 0.2% 2 0.7% 4 0.3% 386G>A G85E 3 0.2% 3 0.2% 3849+10kbC>T 3 0.2% 3 0.2% Unidentified Unidentified 41 3.2% 11 4.0% 52 3.4% Total Total 1262 100.0% 278 100.0% 1540 100.0% Dublin cohort Cork cohort Ireland Amino acid change Nucleotide change We noted similar high frequencies of the F508del and G551D mutations in the three cohorts studied.
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ABCC7 p.Asn1303Lys 12815607:98:393
status: NEW
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115 We concluded that western Brittany presented a specific mutation spectrum (1078delT, G551D, 4005+1G>A, W846X2), whereas the eastern part of the region showed a spectrum of mutations more similar to that generally observed in France (N1303K, Y1092X, 2789+5G>A, etc).
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ABCC7 p.Asn1303Lys 12815607:115:233
status: NEW
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PMID: 12865275 [PubMed] Ahmed N et al: "Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas."
No. Sentence Comment
309 Table 2 Genotype classification according to the functional consequences of CFTR gene mutations Pancreatic status Class I Class II Class III Class IV Class V PS F1 , 875+1G→C(2) F, F (1) F, G551D (1) F, R117H (11) F,3849+10kbC→T (5) F, G85E2 (1) F, R347H (3) F,3272-26A→G (4) F, S1251N (2) F,A445E (3) F, D614G (1) F,P574H (2) F, R347P (1) F,3120G>A (1) R117H,R117H (1) F, 5T (8) F, L1335P (1) F,2789+5G→A (1) F,P67L (1) F,R347P/R347H (1) F,V232D(2) R334W, R334W(1) PS→PI F,3659delC (1) F,F (15) F,G551D (1) F, I1234V (1) F,2184insA (1) F,R560T (1) PI F, G542X (27) F,F (365) F, G551D (28) F, 621+1G→T (13) F, R560T (7) F,R553X (7) F, N1303K (9) F, R1162X (6) F,L1077P (2) F, 3659delC (5) F, I48T (1) F, 1717-1G→A (5) F,A559T (1) F, W1282X (5) F, G85E2 (2) F, 711+1G→T (5) G551D,G551D(1) F,2184delA(4) F,H199R (1) W1282X,W1282X (4) F,I1072T(1) F,Y1092X (3) F,S549 (R75Q) (1) F,556delA (3) F, Q493X (3) F,4016InsT (3) F, 3120+1G→A (2) F, G551D/R553X (2) F,Q814X(2) F,1154insTC (2) F,441delA (1) F, 4326delTC (1) F,Q552X(1) F,3007delG (1) F,2184insA (1) F, 4010del4 (1) F,3905insT (1) F,1078delT(1) F,E1104X (1) F,3876delA (1) F,4374+1G→T (1) F,E585X (1) F, E60X (1) CFTR, cystic fibrosis transmembrane regulator; PI, pancreatic insufficiency; PS, pancreatic sufficiency.
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ABCC7 p.Asn1303Lys 12865275:309:677
status: NEW
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PMID: 12881448 [PubMed] Malehorn DE et al: "Detection of cystic fibrosis mutations by peptide mass signature genotyping."
No. Sentence Comment
138 ⌬b 3 R Y 9863.78 G85E SerϾPhe 9923.90 Y 60.12 4.1 R N 7047.69 R117H AlaϾVal 7075.76 N 28.07 4.2 R Y 11161.32 lI48T AsnϾSer 11134.32 Y -27.00 621ϩ1 GϾT TyrϾTAA 6513.09 N -4648.23 5 R Y 11081.45 711ϩ1 GϾT ThrϾAsn 11094.48 Y 13.03 7.1 R N 7383.08 1078⌬T frameshift 9201.10 Y 1818.02 7 R Y 12233.9 R334W ArgϾGln 12205.87 Y -28.03 R347P ArgϾGly 12134.79 Y -99.11 9 F Y 14049.68 A455E AlaϾGlu 14107.74 Y 58.06 10.2 R Y 10525.57 ⌬I507 ⌬ Asp 10410.50 Y -115.07 ⌬F508 ⌬ Asp & LysϾAsn 10396.43 Y -129.14 11.2 F Y 11173.32 1717-1 GϾA GlyϾArg 11272.46 Y 99.14 G542X TrpϾLeu 11100.27 Y -73.05 G551D no change 11173.32 Y 0.00 R553X ThrϾMet 11203.42 Y 30.10 R560T no change 11173.32 Y 0.00 11 F N 8465.27 1717-1 GϾA no change 8465.27 N 0.00 G542X GlyϾTGA 6584.17 N -1881.10 G551D GlyϾAsp 8523.33 N 58.06 R553X ArgϾTGA 7541.18 N -924.09 R560T ArgϾThr 8410.21 N -55.06 12 F Y 10372.51 1898ϩ1 GϾA GlyϾAsp 10430.57 Y 58.06 13.2A R Y 10103.23 2184⌬A frameshift 8726.91 N -1376.32 14B R Y 9291.17 2789ϩ5 GϾA LeuϾPhe 9325.21 Y 34.04 16 F N 9398.67 3120ϩ1 GϾA ValϾIle 9412.72 N 14.05 19 F Y 17455.96 R1162X ArgϾTGA 6280.13 N -11175.83 3659⌬C frameshift 9650.06 N -7805.90 19i F Y 9699.9 3849ϩ10kB CϾT ArgϾTGA 7131.04 N -2568.86 20 F N 11125.48 W1282X TrpϾTGA 9370.40 N -1755.08 21 F Y 11183.44 N1303K AsnϾLys 11197.54 Y 14.10 a Denotes the directionality of exonic sequence when expressed as peptide.
X
ABCC7 p.Asn1303Lys 12881448:138:1543
status: NEW
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181 The heterozygous mutations depicted are as follows: (A), exon 3 wt/G85E; (B), exon 4.1 wt/R117H; (C), exon 4.2 wt/I148T; (D), exon 4.2 wt/621 ؉ 1G>T; (E), exon 5 wt/711 ؉ 1G>T; (F), exon 7.1 wt/1078⌬T; (G), exon 7 wt/R334W; (H), exon 7 wt/R347P; (I), exon 9 wt/A455E; (J), exon 10.2 wt/⌬I507; (K), exon 10.2 wt/⌬F508; (L), exon 11.2 wt/1717-1G>A; (M), exon 11 wt/G542X; (N), exon 11 wt/G551D; (O), exon 11 wt/R553X; (P), exon 11 wt/R560T; (Q), exon 12 wt/1898 ؉ 1G>A; (R), exon 13.2A wt/2184⌬A; (S), exon 14B wt/2789 ؉ 5G>A; (T), exon 16 wt/3120 ؉ 1G>A; (U), exon 19 wt/R1162X; (V), exon 19 wt/3659⌬C; (W), intron 19 wt/3849 ؉ 10kbC>T; (X), exon 20 wt/W1282X; (Y), exon 21 wt/N1303K. typical yield of purified protein was 1-30 ␮g/test well, depending on the analyte species.
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ABCC7 p.Asn1303Lys 12881448:181:747
status: NEW
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PMID: 12906319 [PubMed] Wallis C et al: "Atypical cystic fibrosis--diagnostic and management dilemmas."
No. Sentence Comment
176 She was found to have a disease-associated mutation in each CFTR gene (N1303K and R117H associated with the 7T variant in intron 8).
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ABCC7 p.Asn1303Lys 12906319:176:71
status: NEW
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PMID: 12939655 [PubMed] Perri F et al: "Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the serine protease inhibitor, Kazal type 1 (SPINK1) gene in patients with alcoholic chronic pancreatitis."
No. Sentence Comment
33 Mutation screening of the CFTR gene The 31 most frequent mutations (F508del, I507del, G551D, G542X, N1303K, 1717-1G4A, W1282X, R553X, R347P, R347H, R334W, 3849+10kb C4T, R117H, 621+1G4T, A455E, S549N, R560T, S549R, V520F, Q493X, 3849+ 4A4G, 1078delT, R1162X, 3659delC, 3905insT, Y122X, 2183delAA4G, 2789+5G4A, 1898+1G4A, 711+1G4T, and G85E) were examined with the polymerase chain reaction (PCR) followed by an oligonucleotide ligation assay (OLA, Applied Biosystems, Foster City, CA, USA) and finally a sequence-coded separation.
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ABCC7 p.Asn1303Lys 12939655:33:100
status: NEW
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PMID: 12940920 [PubMed] Rowntree RK et al: "The phenotypic consequences of CFTR mutations."
No. Sentence Comment
31 The majority of the other CFTR mutations are very rare with only four other mutations (G542X, N1303K, G551D and W1282X) having overall frequencies above 1%.
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ABCC7 p.Asn1303Lys 12940920:31:94
status: NEW
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PMID: 12952861 [PubMed] Lee JH et al: "A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases."
No. Sentence Comment
15 Several mutations of CFTR, such as F508del, G542X and N1303K, are associated with severe CF phenotypes and display high disease penetrance.
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ABCC7 p.Asn1303Lys 12952861:15:54
status: NEW
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74 CFTR genetic variants analyzed in this study Variations found by TDGS Most common worldwide disease-causing mutations Reported disease-associated microsatellite À8G/C (50 UTR)a R117H (exon 4) T5-7,9 (IVS 8) (16) I125T (exon 4)b 621 þ 1G > T (intron 4) E217G (exon 6a)b F508del (exon 10) 1059C > T (exon 7, A309)a 1717-1G > A (intron 10) M470V (exon 10)b G542X (exon 11) I556V (exon 11)b G551D (exon 11) 2694T/G (exon 14a, T854)b R553X (exon 11) Q1352H (exon 22)b R1162X (exon 19) R1453W (exon 24)b W1282X (exon 20) N1303K (exon 21) Mutation names and nucleotide numbers are presented according to the Cystic Fibrosis Genetic Analysis Consortium (CFGAC; www.genet.sickkids.on.ca/).
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ABCC7 p.Asn1303Lys 12952861:74:525
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160 However, over 95% of the three most common CF-causing mutations, F508del, G542X and N1303K, arise from this haplotype.
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ABCC7 p.Asn1303Lys 12952861:160:84
status: NEW
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PMID: 14501614 [PubMed] Efrati O et al: "Liver cirrhosis and portal hypertension in cystic fibrosis."
No. Sentence Comment
92 Unauthorized reproduction of this article is prohibited. Table 2 Details of the 10 cystic fibrosis patients with portal hypertension Pulmonary function test Symptoms Liver Patient of portal synthetic Procedures number Sex Mutation FEV1 FVC hypertension function (year) 1 M W1282X/W1282X 50% 55% H,V Abnormal Splenectomy & splenorenal shunt (`63) 2 F A¨ F508/G542X 75% 90% H,V Abnormal Portacaval end to side shunt (`77) 3 M G542X/W1282X 82% 92% H,V Abnormal Liver transplantation (`90) 4 M A¨ F508/W1282X 65% 80% H,V,A Abnormal Sclerotherapy & portacaval shunt (`98) 5 M G542X/W1282X 30% 40% H,V,A Abnormal Sclerotherapy & TIPSS (x2): right hepatic to left portal shunt (`99) 6 M A¨ F508/G542X 70% 80% H,V Abnormal Sclerotherapy & portosystemic shunt: superior mesenteric vein to left renal vein (`99) 7 M A¨ F508/A¨ F508 22% 25% H,V,A Abnormal Recurrent sclerotherapy (x5) & TIPSS 8 F W1282X/N1303K 75% 85% H,V,A Abnormal Sclerotherapy 9 M G542X/G542X 65% 70% H,V,A Abnormal Sclerotherapy 10 M A¨ F508/A¨ F508 55% 85% H,V Borderline Sclerotherapy M, male; F, female; FEV1, forced expiratory volume in 1s; FVC, forced vital capacity; H, hypersplenism; V, varices; A, ascites; TIPSS, transjugular intrahepatic portosystemic shunt.
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ABCC7 p.Asn1303Lys 14501614:92:918
status: NEW
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PMID: 14562574 [PubMed] Morinville V et al: "Genetic disorders of the pancreas."
No. Sentence Comment
80 Ten of twenty-seven (37%) had at least one abnormal CFTR allele (deltaF508, R117H, N1303K, and the 5T allele), none with criteria diagnostic of cystic fibrosis.
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ABCC7 p.Asn1303Lys 14562574:80:83
status: NEW
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84 Mutations of CFTR include: deltaF508, R117H, D1152H, P574H, 3120 G > A, 621 + 1 G > T, G1069R, N1303K.
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ABCC7 p.Asn1303Lys 14562574:84:95
status: NEW
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PMID: 14576497 [PubMed] Pezzilli R et al: "Mutations of the CFTR gene in pancreatic disease."
No. Sentence Comment
59 The 29 Mutations and the Tn Polymorphism Which Can Be Detected by INNO-LiPA Assays Mutation Exon/Intron (i) E60X, G85E, 394delTT 3 621 + 1G > T, R117H (i) 4, 4 711 + 5G > A (i) 5 1078delT, R347P, R334W 7 A455E, Tn (i) 8, 9 ⌬F508, ⌬I507 10 G542X, 1717-1 G > A, G551D, R553X, R560T, Q552X (i) 10, 11 2183AA > G, 2184del A, 2143delT 13 2789 + 5G > A (i) 14b R1162X, 3659delC 19 3849 + 10kbC > T (i) 19 3905insT, W1282X, S1251N 20 N1303K 21 Group 3: pancreatic cancer CFTR gene mutations were identified only in 1 of the 18 patients (5.6%) with this cancer.
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ABCC7 p.Asn1303Lys 14576497:59:441
status: NEW
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PMID: 14586256 [PubMed] Reboul MP et al: "Isolated idiopathic chronic pancreatitis associated with a compound heterozygosity for two mutations of the CFTR gene."
No. Sentence Comment
60 Patient no 2 is a compound heterozygote for R117H and N1303K: her phenotype is that of a moderate cystic fibrosis as shown by respiratory signs and an abnormal nasal potential difference in the context of a borderline sweat test.
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ABCC7 p.Asn1303Lys 14586256:60:54
status: NEW
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80 Patient CFTR no PolyT genotype Sex genotype Age (years) Sweat chloride (mmol/L) Anamnestic features known to be associated with atypical CF Reference 1 F508del/R117H 9T/7T M 45 29 CBAVD [4] 2 N1303K/R117H 9T/7T F n.a. 37 bronchiectasis, sinusitis, positive NPD [5] 3 R1162X/2789+5G>A 7T/7T F n.a. 108 chronic cough [5] 4 I336K/R75Q 7T/7T F 26 26 nasal polyposis [7] 5 F508del/L997F 9T/7T M 17 24 none [11] 6 3849+10kbC>T/3878delG 7T/7T M 14 n.a. none [11] 7 S1235R/L997F 5T/7T M 27 25 none [11] 8 F508del/R117H n.a. M 45 29 CBAVD, smooth P. aeruginosa [12] 9 F508del/I1027T n.a. F 32 59 none [12] 10 F508del/D1152H n.a. M 8 62 none [12] 11 F508del/D1152H n.a. F 15 32 none [12] 12 F508del/P574H n.a. F 26 81 sinus surgery, S. aureus, S. maltophilia [12] 13 F508del/3120G>A n.a. F 40 n.a. n.a. [12] 14 F508del/G1069R n.a. M 16 n.a. n.a. [12] 15 G542X/S1235R 7T/7T M 35 15 none [this study] n.a.: not available.
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ABCC7 p.Asn1303Lys 14586256:80:192
status: NEW
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PMID: 14641997 [PubMed] Raskin S et al: "High allelic heterogeneity between Afro-Brazilians and Euro-Brazilians impacts cystic fibrosis genetic testing."
No. Sentence Comment
11 Although the major mutation causing CF accounts for 66% of mutant chromosomes screened worldwide, at least 1,000 sequence alterations associated with the disease have been identified in the CFTR gene during the past years, and their frequencies vary between populations (Tsui, 1990, 1992; Cystic Fibrosis Genetic AnalysisConsortium,1994, 1999).Previously, we have shown allelic heterogeneity in Brazilian CF patients of European origin by screening for DF508 and another four common worldwide mutations (G542X, N1303K, G551D, and R553X).
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ABCC7 p.Asn1303Lys 14641997:11:511
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63 FREQUENCIES OF 70 CFTR MUTATIONS IN DIFFERENT STATES OF BRAZIL, BY CONTINENTA L GROUP CFTR mutations SC PR MG detected n n n n % n % N % DF508 53 39 54 146 47.1 8 10.5 154 39.9 G542X 6 9 8 23 7.4 1 1.3 24 6.2 R1162X 9 2 4 15 4.8 2 2.6 17 4.4 N1303K 5 5 0 10 3.2 0 0 10 2.6 R334W 5 1 4 10 3.2 0 0 10 2.6 G85E 2 2 4 8 2.6 1 1.3 9 2.3 1717-1G®A 1 3 2 6 1.9 0 0 6 1.6 W1282X 4 1 1 6 1.9 0 0 6 1.6 3849110kbC®T 1 3 1 5 1.6 0 0 5 1.3 R553X 0 2 0 2 0.7 0 0 2 0.5 1812-1G®A 0 1 3 4 1.3 1 1.3 5 1.3 2183AA®G 2 1 0 3 1.0 0 0 3 0.8 312011G®A 0 0 2 2 0.7 2 2.6 4 1.0 Y1092X 0 1 1 2 0.7 1 1.3 3 0.8 G551D 0 0 0 0 0 0 0 0 0 W1089X 0 0 1 1 0.3 0 0 1 0.3 6211G®T 0 1 0 1 0.3 0 0 1 0.3 Q1238X 0 1 0 1 0.3 0 0 1 0.3 711-1G®T 0 1 0 1 0.3 0 0 1 0.3 R347P 1 0 0 1 0.3 0 0 1 0.3 189811G®A 1 0 0 1 0.3 0 0 1 0.3 I507 0 0 1 1 0.3 0 0 1 0.3 Subtotal 91 73 86 250 80.7 16 21.1 266 68.9 Alleles with CFTR 5 27 28 60 19.4 60 79.0 120 31.1 mutations not detected Total 96 100 114 310 100.0 76 100.0 386 100.0 Detection rate (%) 94.8 73.0 75.4 250 80.7 16 21.1 266 68.9 The following 70 CFTR mutations were selected and tested on the basis of frequency in various populations, known association with CF, or predicted deleterious effect on the CFTR protein product; DF508, G542X, N1303K, G551D, R553X, DI507, A455E, A559T, C524X, D1270N, E60X, G178R, G330X, G85E, 2307insA, I148T, K710X, P574H, Q1238X, Q493X, Q890X, R1158X, R1162X, R117H, R334W, R347H, R347P 2307insA, I148T, K710X, P574H, Q1238X, Q493X, Q890X, R1158X, R1162X, R117H, R334W, R347H, R347P 2307insA, 1148T, K710X, P574H, Q1238X, Q493X, Q890X, R1158X, R1162X, R117H, R334W, R347H, R347P, R352Q, R560T, S1196X, S1255X, S364P, S549N, S549R, V520F, W1089X, W1282X, W1310X, W1316X, Y1092X, Y122X, Y563D, 1078delT,1677delTA,1717-1G-A,1812-1G-A,1898 1 1G-A, 2043delG,2183delAA-G, 2184delA, 2789 1 5G-A, 2869insG, 2909delT, 3120 1 1G-A, 3120G-A, 3358delAC, 3659delC, 3662delA, 3750delAG, 3791delC, 3821delT, 3849 1 10KbC-T, 3849 1 4A-G, 3905insT, 405 1 1G-A, 444delA, 556delA, 574delA, 621 1 1G-T, and 711 1 1G-T. aSC, Santa Catarina State; PR, Parana State; MG, Minas Gerais State; n, number of chromosomes.
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ABCC7 p.Asn1303Lys 14641997:63:242
status: NEW
X
ABCC7 p.Asn1303Lys 14641997:63:1289
status: NEW
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PMID: 14662004 [PubMed] Zeitlin PL et al: "Emerging drug treatments for cystic fibrosis."
No. Sentence Comment
53 The ∆F508 mutation and others such as N1303K or P574H [26], which are also misprocessed in the ER, have been grouped together as Class 2 mutations in CFTR [27].
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ABCC7 p.Asn1303Lys 14662004:53:45
status: NEW
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88 Class of mutation Molecular mechanism Pancreatic status (if known) Examples 1 No CFTR protein synthesis PI W1282X, G542X, R553X, 621 + 1 G→T, 1717-1 G→A, 3905insT, 394delTT 2 Abnormal CFTR processing and trafficking PI ∆F508, N1303K, P574H 3 Defective CFTR regulation (normal trafficking) PI G551D, G551S, G1349D, S1255P 4 Decreased CFTR chloride conductance PS R117H, R334W, R347P, P547H 5 Reduced synthesis and trafficking of normal CFTR PS A455E, 3849 + 10kb C→T, (5T) 6A Reduced apical stability PI S1455X, Q1412S, 4326delTC, 4279insA 6B Defective regulation of other ion channels PI G551D Note that the G551D is placed in Class 3 for defective regulation and Class 6B for defective regulation of the outwardly rectifying chloride channel.
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ABCC7 p.Asn1303Lys 14662004:88:247
status: NEW
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PMID: 14670800 [PubMed] Becker MN et al: "Cytokine secretion by cystic fibrosis airway epithelial cells."
No. Sentence Comment
48 1 3 TD 37 M 1 3 24 M ⌬F508/W1282X 1 4 NTD 19 M 1 4 25 M W1282X/N1303K 1 5 NTD 40 F 1 5 20 M ⌬F508/⌬F508 1, 2, 3, 5 6 COPD 60 M 1, 3, 4, 5 6 41 M ⌬F508/⌬F508 1, 2, 4, 5 7 NTD 23 M 2, 3 7 10 M ⌬F508/⌬F508 2 8 TD 36 F 2, 3 8 37 M Not genotyped 2 9 TD 21 M 2 9 28 M ⌬F508/⌬F508 2, 3, 4, 5 10 NTD 45 M 2 10 18 F ⌬F508/⌬F508 2, 4, 5 11 NTD 42 M 2 11 29 M ⌬F508/621ϩ1GϾT 3 12 NTD 22 M 2 12 47 F Not genotyped 3 13 COPD 57 M 3, 4 13 42 M ⌬F508/?
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ABCC7 p.Asn1303Lys 14670800:48:70
status: NEW
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49 3 14 NTD 51 F 3 14 30 F Not genotyped 3 15 TD 48 F 3 15 22 F ⌬F508/⌬F508 3, 4 16 NTD 45 F 3 16 42 M 2789ϩ5GϾA/N1303K 4 17 NTD 28 M 4 17 32 F ⌬F508/⌬F508 4 18 NTD 46 M 4 18 27 F ⌬F508/G542X 4 19 TD 20 M 4 19 21 F ⌬F508/G85E 4 20 PF 63 M 4 20 26 F N1303K/?
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ABCC7 p.Asn1303Lys 14670800:49:136
status: NEW
X
ABCC7 p.Asn1303Lys 14670800:49:300
status: NEW
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PMID: 14739679 [PubMed] Farriaux JP et al: "Neonatal screening for cystic fibrosis: France rises to the challenge."
No. Sentence Comment
114 In its present version, the kit allows screening for 20 CFTR gene mutations (F508del, G542X, N1303K, 1717-1G>A, G551D, W1282X, R553X, I507del, 1078delT, 2183AA>G, 3849 þ 10kbC>T, R1162X, 621 þ 1G>T, R334W, R347P, 3659delC, R117H, S1251N, E60X, A455E) in one workday; moreover, it does not require any speci'c equipment.
X
ABCC7 p.Asn1303Lys 14739679:114:93
status: NEW
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PMID: 14963811 [PubMed] Luzardo G et al: "Cystic fibrosis in Uruguay."
No. Sentence Comment
36 The CFTR mutations were detected by using one or more of the following methods: a) Reverse hybridization technique for eight mutations frequent in Europe (∆F508, G542X, N1303K, 1717-1G→A, W1282X, G551D, R553X and ∆I507), using a commercial kit from Inno Lipa CF2, Innogenetics, Belgium.
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ABCC7 p.Asn1303Lys 14963811:36:176
status: NEW
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42 RESULTS Genetic analysis led to the detection of 15 different mutations: ∆F508, G542X, R1162X, G85E, N1303K, R334W, R75Q, R74W, D1270N, W1282X, ∆I507, 2789+5G→A, R1066C, R553X and -816C/T.
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ABCC7 p.Asn1303Lys 14963811:42:108
status: NEW
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47 Mutation Cumulative (%)%N ∆F508 G542X R1162X G85E N1303K R334W R75Q Other mutations* Unknown 42 6 3 3 3 2 2 13 30 40.4 5.7 2.9 2.9 2.9 1.9 1.9 12.5 28.9 40.4 46.1 49.0 51.9 54.9 56.7 58.6 71.1 99.9 *R74W, D1270N, W1282X, ∆I507, 2789+5G→A, R1066C, -816C/T, R553X, 5T (3 cases associated to other mutations, 2 cases without known second mutation).
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ABCC7 p.Asn1303Lys 14963811:47:57
status: NEW
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59 Genotypes N Percent ∆F508/∆F508 ∆F508/R1162X ∆F508/G85E ∆F508/G542X ∆F508/5T ∆F508/R334W ∆F508/1303X ∆F508/R1066C ∆F508/Unknown ∆I507/2789+G-A R74W/D1270N N1303K/G542X N1303K/R553K -816C-T/5T 5T/Unknown G542X/Unknown R75Q/Unknown W1282X/Unknown Unknown/Unknown 8 3 3 3 2 2 1 1 11 1 1 1 1 1 2 2 2 1 6 15.4 5.8 5.8 5.8 3.9 3.9 1.9 1.9 21.2 1.9 1.9 1.9 1.9 1.9 3.9 3.9 3.9 1.9 11.5 All individuals had pulmonary symptoms.All those carrying the ∆F508/∆F508 genotype had pancreatic insufficiency.
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ABCC7 p.Asn1303Lys 14963811:59:232
status: NEW
X
ABCC7 p.Asn1303Lys 14963811:59:245
status: NEW
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89 We have also observed differences in the distribution and frequencies of non-∆F508 mutations between Uruguayans and patients from other LatinAmerican countries, in particular compared to theArgentinean population.AmongArgentine CF patients, seven mutations (∆F508, G542X, W1282X, N1303K, 17171G→A, R553X, R1162X) constituted 67.5% of the observed alleles (Chertkoff et al., 1997), while in our population 15 mutations corresponded to a similar cumulative percentage (71%).
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ABCC7 p.Asn1303Lys 14963811:89:294
status: NEW
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90 There is an agreement between the most common Uruguayan CFTR mutations (∆F508, G542X, R1162X, N1303K, R334W, W1282X and R553X) and those reported in the geographical regions from where most Uruguayans`ancestors originated, namely, Spain, the Canary Islands, Italy and the Basque regions.
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ABCC7 p.Asn1303Lys 14963811:90:101
status: NEW
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PMID: 14998948 [PubMed] Danziger KL et al: "Improved detection of cystic fibrosis mutations in infertility patients with DNA sequence analysis."
No. Sentence Comment
59 Polyacrylamide gels were analysed for the presence of mutations following staining in ethidium bromide (EtBr) and image capture under UV using the Gel Doc 1000 system Table I. List of CFTR mutations included in common mutation panels American College of Medical Genetics CF panel (25 mutations) DF508 G542X G551D R117H W1282X N1303K R1162X 3849+10kbC®T DI507 R553X 1717-1G®A 621+1G®T R560T 3659delC 3120+1G®A I148T G85E R334W A455E 1898+1G®A 2148delA 711+1G®T 2789+5G®A R347P 1078delT Six additional mutations and one polymorphism in UCSF panel (31 mutations) Y1092X R347H 3849+4 Q493X 3905insT S549N F508C (polymorphism) (BioRad).
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ABCC7 p.Asn1303Lys 14998948:59:326
status: NEW
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PMID: 15010427 [PubMed] Strom CM et al: "Direct visualization of cystic fibrosis transmembrane regulator mutations in the clinical laboratory setting."
No. Sentence Comment
200 In a second comparison with the Applera CF OLA, Ver. 3.0, we analyzed 1076 samples, including 3 fixed positive controls (⌬F508/⌬F508, 5T/WT, and N1303K/WT) and 1 rotating control of known genotype.
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ABCC7 p.Asn1303Lys 15010427:200:159
status: NEW
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203 In this comparison, there were 19 ⌬F508 heterozygous patient samples, 3 I148T heterozygous samples, 3 R117H heterozygous and 1 R117H homozygous samples, 2 W1282X heterozygous samples, and 1 heterozygous patient sample each for G551D, R553X, R1162X, and 3849 ϩ 10kBCϾT, for a total of 36 mutant alleles. Additional mutant alleles detected for this study included fixed controls ⌬F508 homozygous, 5T/WT, and a N1303K heterozygous sample on all plates, and one heterozygous sample each for R560T, G542X, R553X, W1282X, 2184delA, G85E, I148T, 621 ϩ 1GϾT, R334W, R117H, 1078delT, and 1717-1GϾA as rotating controls.
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ABCC7 p.Asn1303Lys 15010427:203:434
status: NEW
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PMID: 15047968 [PubMed] King PT et al: "Role of CFTR mutations in adult bronchiectasis."
No. Sentence Comment
230 The patients were screened for the 10 most common mutations in the local population (DF508, D1507, V520F, G542X, G551D, R553X, R117H, 621+1GRT, A455E and N1303K) responsible for 82% of cases of CF and the 5T mutation by previously published methods.7 8 Ethical approval for the project was obtained from the ethics committee at MMC.
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ABCC7 p.Asn1303Lys 15047968:230:154
status: NEW
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PMID: 15070876 [PubMed] Dayangac D et al: "Mutations of the CFTR gene in Turkish patients with congenital bilateral absence of the vas deferens."
No. Sentence Comment
35 We next screened for six further CFTR gene mutations of the coding region and ¯anking intron sequences by previously described restriction-enzyme based methods: G85E, D110H, R347H, 2789+5G®A, D1152H, N1303K (DoÈrk et al., 1994a, 1997).
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ABCC7 p.Asn1303Lys 15070876:35:210
status: NEW
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PMID: 15084222 [PubMed] D'Apice MR et al: "Molecular analysis using DHPLC of cystic fibrosis: increase of the mutation detection rate among the affected population in Central Italy."
No. Sentence Comment
67 This CF mutation was identified in a patient who carries the N1303K (4041 C to G) mutation on the maternal CF chromosome.
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ABCC7 p.Asn1303Lys 15084222:67:61
status: NEW
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89 Table 1: Primers and DHPLC (oven temperature, gradient) analysis conditions for 6b and 9 exons of the CFTR gene exon Primer 5' → 3' Amplicon length Oven temp (°C) % B buffer start/end 6b F - CAGAGATCAGAGAGCTGGG 323 56 55/63 R - GAGGTGGAAGTCTACCATGA 9 F - GGGATTTGGGGAATTATTTG 279 55 54/62 R - TCTCCAAAAATACCTTCCAG Table 2: CF mutations identified in cohort of 290 patients from the Central Italy Mutation Nucleotide change Exon/intron N % Method delF508 1652delCTT 10 328 56.36 INNO-LiPA, DHPLC N1303K 4041 C to G 21 51 8.76 INNO-LiPA, DHPLC G542X 1756 G to T 11 42 7.21 INNO-LiPA, DHPLC W1282X 3978 G to A 20 15 2.60 INNO-LiPA, DHPLC S549R 1779 T to G 11 8 1.37 DHPLC 621+1G-T 621+1 G to T Intron 4 7 1.20 INNO-LiPA, DHPLC 1717-1G-A 1717-1 G to A Intron 10 5 0.86 INNO-LiPA, DHPLC G85E 386 G to A 3 4 0.69 INNO-LiPA, DHPLC R553X 1789 C to T 11 4 0.69 INNO-LiPA, DHPLC H139R 548 A to G 6a 3 0.51 DHPLC R347P 1172 G to C 7 3 0.51 INNO-LiPA, DHPLC L1065P 3326 T to C 17b 3 0.51 DHPLC L1077P 3362 T to C 17b 3 0.51 DHPLC S4X 143 C to A 1 2 0.34 DHPLC D110H 460 G to C 4 2 0.34 DHPLC R334W 1132 C to T 7 2 0.34 INNO-LiPA, DHPLC M348K 1175 T to A 7 2 0.34 DHPLC 1259insA 1259 ins A 8 2 0.34 DHPLC S549N 1778 G to A 11 2 0.34 DHPLC L558S 1805 T to C 11 2 0.34 DHPLC 2183+AA-G 2183 A to G and 2184 del A 13 2 0.34 INNO-LiPA, DHPLC 2789+5G-A 2789+5 G to A Intron 14b 2 0.34 INNO-LiPA, DHPLC R1066C 3328 C to T 17b 2 0.34 DHPLC 3667ins4 3667insTCAA 19 2 0.34 DHPLC S42F 257 C to T 2 2 0.34 DHPLC R117L 482 G to T 4 1 0.17 DHPLC H199R 728 A to G 6a 1 0.17 DHPLC R334L 1133 G to T 7 1 0.17 DHPLC T338I 1145 C to T 7 1 0.17 DHPLC G551D 1784 G to A 11 1 0.17 INNO-LiPA, DHPLC Q552X 1786 C to T 11 1 0.17 INNO-LiPA, DHPLC D614G 1973 A to G 13 1 0.17 DHPLC A1006E 3149 C to A 17a 1 0.17 DHPLC 4016insT 4016 ins T 21 1 0.17 DHPLC 4040delA 4040 del A 21 1 0.17 DHPLC 4167del7 4167 delCTAAGCC 22 1 0.17 DHPLC Detected 511 88.10 Unknown 69 11.90 Total 580 100.00 N = number of CF chromosomes; % = frequency.
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ABCC7 p.Asn1303Lys 15084222:89:509
status: NEW
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PMID: 15084988 [PubMed] Naruse S et al: "A finger sweat chloride test for the detection of a high-risk group of chronic pancreatitis."
No. Sentence Comment
50 The DNA samples were analyzed using an amplification refractory mutation system kit for 20 common major CFTR mutations (E60X, R117H, R334W, R347P, A455E, ⌬I507, ⌬F508, G542X, G551D, R553X, 621+1G>T, 1078delT, R1162X, S1251N, W1282X, N1303K, 1717-1G>A, 2183AA>G, 3659delC, 3849+10kbC>T) (Elucigene CF 20, AstraZeneca Diagnostics, Abingdon, UK) following the standard procedures recommended by the manufacturer.
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ABCC7 p.Asn1303Lys 15084988:50:247
status: NEW
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PMID: 15121783 [PubMed] Fujiki K et al: "Genetic evidence for CFTR dysfunction in Japanese: background for chronic pancreatitis."
No. Sentence Comment
218 The 20 most common CF mutations (E60X, R117H, R334W, R347P, A455E, DI507, DF508, G542X, G551D, R553X, 621+1GRT, 1078delT, R1162X, S1251N, W1282X, N1303K, 1717-1GRA, 2183AARG, 3659delC, and 3849+10kbCRT) were tested by an Elucigene CF20 kit (AstraZeneca Diagnostics, Abingdon, Oxfordshire, UK).
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ABCC7 p.Asn1303Lys 15121783:218:146
status: NEW
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PMID: 15121798 [PubMed] Ogino S et al: "Bayesian risk assessment for autosomal recessive diseases: fetal echogenic bowel with one or no detectable CFTR mutation."
No. Sentence Comment
185 If a relative of parent A or parent B is affected or an obligate carrier, this table can still be applied when neither that relative nor any other family member has been tested. Table 3 Summary of carrier frequencies for cystic fibrosis, overall mutation detection rates by the ACMG 25 mutation panel, and frequencies of major mutations for each major ethnic group (adapted from Richards et al. and Bobadilla et al.)4 18 Ethnic group Cystic fibrosis carrier frequency Overall mutation detection rate by ACMG CFTR 25 mutation panel (%) Frequency DF508 among all disease alleles (%) Other major mutations (%)* Non-Hispanic 1/25 90 70 G542X 2.4 Caucasian G551D 2.1 W1282X 1.4 N1303K 1.3 Ashkenazi Jewish 1/25 97 30 W1282X 48 G542X 9.0 3849+10kbCRT 6.0 N1303K 3.0 1717-1GRA 1.0 African-American 1/65 69 48 3120+1GRA 12 2307insA 2.0 A559T 2.0 R553X 2.0 DF311 2.0 G480C 1.4 405+3ARC 1.4 S1255X 1.4 Hispanic American 1/46 57 46 G542X 5.4 3849+10kbCRT 2.3 R1162X 1.6 R334W 1.6 Asian American 1/90 ?
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ABCC7 p.Asn1303Lys 15121798:185:673
status: NEW
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ABCC7 p.Asn1303Lys 15121798:185:749
status: NEW
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PMID: 15173476 [PubMed] Comeau AM et al: "Population-based newborn screening for genetic disorders when multiple mutation DNA testing is incorporated: a cystic fibrosis newborn screening model demonstrating increased sensitivity but more carrier detections."
No. Sentence Comment
79 The 16-mutation panel included ⌬F508, R117H, G551D, G542X, W1282X, N1303K, R334W, 621 ϩ 1GϾT, R553X, ⌬I507, 1717-1GϾA, R347P, R560T, 3849 ϩ 10kbCϾT, A455E, and S549N.
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ABCC7 p.Asn1303Lys 15173476:79:74
status: NEW
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159 Genotypes and Frequencies Observed in 112 CF-Affected Infants First Mutation Second Mutation N ⌬F508 ⌬F508 55 ⌬F508 R117H 7* ⌬F508 G551D 4 ⌬F508 N1303K 3 ⌬F508 W1282X 3 ⌬F508 G542X 2 ⌬F508 1898 ϩ 1 G Ͼ A 2 G85E R117C 2 ⌬F508 1717-GϾA 1 ⌬F508 3849 ϩ 10kbC Ͼ T 1 ⌬F508 R1066C 1 ⌬F508 Y1092X 1 ⌬F508 L206W 1 ⌬F508 R560T 1 ⌬F508 1152H 1 ⌬F508 621 ϩ 1G Ͼ T 1 R117H G551D 1 R117H G85E 1 G551D 2789 ϩ 5GϾA 1 G551D R117C 1 G85E 711 ϩ 1GϾT 1 W1282X 3849 ϩ 10kbCϾT 1 R553X 2183AAϾG 1 A455E S549R 1 ⌬F508 Unknown† 13 N1303K Unknown 2 G542X Unknown 1 Unknown Unknown 2 * Includes 1 of the false-negative screens.
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ABCC7 p.Asn1303Lys 15173476:159:180
status: NEW
X
ABCC7 p.Asn1303Lys 15173476:159:716
status: NEW
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PMID: 15176679 [PubMed] Decaestecker K et al: "Genotype/phenotype correlation of the G85E mutation in a large cohort of cystic fibrosis patients."
No. Sentence Comment
137 In patients carrying mutations like F508del, N1303K and W1282X, which correlate with a severe phenotype, w95% have PI [21].
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ABCC7 p.Asn1303Lys 15176679:137:45
status: NEW
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PMID: 15233679 [PubMed] Choudari CP et al: "Risk of pancreatitis with mutation of the cystic fibrosis gene."
No. Sentence Comment
45 ( F508, G551D, R553X, W1282X, N1303K, R117H, Delta I507, 621+1G- >T, R560T, 1717-1G->A, 711+1G->T, and R1162X; Nichols Institute, Nichols Institute Reference Laboratories, California).
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ABCC7 p.Asn1303Lys 15233679:45:30
status: NEW
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PMID: 15238770 [PubMed] Felley C et al: "The role of CFTR and SPINK-1 mutations in pancreatic disorders in HIV-positive patients: a case-control study."
No. Sentence Comment
42 Samples were tested: (i) for 20 common CFTR mutations (delF508, 621+1G.T, G542X, 3849+10kbC.T, N1303K, 3659delC, 1717-1G.A, 1078delT, W1282X, R347P, G551D, A455E, R553X, S1251N, R1162X, delF507, R334W, 2183AA.G, R117H, and E60X; Elucigene CF20; Orchid Biosciences, Abingdon, UK); (ii) for the CFTR IVS8 5T variant (Elucigene CF Poly-T; Orchid); and (iii) for the SPINK-1 N34S polymorphism, by poly- Copyright (c) Lippincott Williams & Wilkins.
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ABCC7 p.Asn1303Lys 15238770:42:95
status: NEW
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PMID: 15238778 [PubMed] Ockenga J et al: "The puzzle of genes and environmental risk factors for disease susceptibility: putting the pieces together."
No. Sentence Comment
11 Approximately 72% of cystic fibrosis patients are homozygous or compound heterozygous for eight mutations of the CFTR regulator gene on chromosome 7: delta F508, G542X, R553X, W1282X, N1303K, 621 + 1G!T, 1717-1G!A, R117H [3]; whereas the deletion delta F508 alone accounts for approximately 66% of mutant cystic fibrosis alleles.
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ABCC7 p.Asn1303Lys 15238778:11:184
status: NEW
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PMID: 15266396 [PubMed] Cardoso H et al: "A low prevalence of cystic fibrosis in Uruguayans of mainly European descent."
No. Sentence Comment
38 *G542X, R1162X, G85E, N1303K, R334W, R75Q, R74W, D1270N, W1282X, ∆I507, 2789+5G->A, R1066C, -816C/T, and R553X. Table 1.
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ABCC7 p.Asn1303Lys 15266396:38:22
status: NEW
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56 *G542X, R1162X, G85E, N1303K, R334W, R75Q, R74W, D1270N, W1282X, ∆I507, 2789+5G->A, R1066C, -816C/T, R553X. Table 2.
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ABCC7 p.Asn1303Lys 15266396:56:22
status: NEW
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PMID: 15297887 [PubMed] Jarzabek K et al: "Cystic fibrosis as a cause of infertility."
No. Sentence Comment
58 CFTR screening includes the most frequent CFTR mutations, for example in the German population: ΔF508, R347P, G542X, S549I, N, R (A→C), G551D, R553X, N1303K, 3849+10kbC→T [11].
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ABCC7 p.Asn1303Lys 15297887:58:163
status: NEW
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PMID: 15334505 [PubMed] Picard E et al: "Familial concordance of phenotype and microbial variation among siblings with CF."
No. Sentence Comment
66 The following genotypes were found among the families: DF508/DF508 (7), W1282X/W1282X (4), N1303K/N1303K (3), DF508/ W1282X (3), W1282X/N1303K (2), DF508/G542X (2), DF508/3849þ10 kb C !
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ABCC7 p.Asn1303Lys 15334505:66:91
status: NEW
X
ABCC7 p.Asn1303Lys 15334505:66:98
status: NEW
X
ABCC7 p.Asn1303Lys 15334505:66:136
status: NEW
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68 A (1), DF508/N1303K (1), W1282X/3849þ10 kb C !
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ABCC7 p.Asn1303Lys 15334505:68:13
status: NEW
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PMID: 15354331 [PubMed] Strom CM et al: "Cystic fibrosis screening: lessons learned from the first 320,000 patients."
No. Sentence Comment
47 Frequency, all tests Frequency, CF mutations (%) delta F508 7610 1:44 75% R117H/7T or 9T 1030 1:325 NAb R117H/5T 103 1:3,254 0.51c W1282X 529 1:625 5.2 G542X 382 1:909 3.8 G551D 278 1:1,250 2.7 N1303K 201 1:1,668 2.0 3849ϩ10kb CϾT 167 1:2,007 1.6 1717-1 GϾA 102 1:3,286 1.0 R553X 102 1:3,286 1.0 621ϩ1 GϾT 98 1:3,420 0.97 2789ϩ5 GϾA 82 1:4,087 0.80 3120ϩ1 GϾA 73 1:4,591 0.72 R1162X 54 1:6,207 0.53 R334W 54 1:6,207 0.53 685E 52 1:6,446 0.51 R560T 52 1:6,446 0.51 Delta I507 51 1:6,572 0.50 711ϩ1 GϾT 40 1:8,380 0.39 1898ϩ1 GϾA 37 1:9,059 0.36 3659 del C 36 1:9,311 0.36 A455E 34 1:9,858 0.33 R347P 33 1:10,158 0.32 2184 del A 14 1:23,943 0.14 1078 del T 6 1:55,867 0.06 a I148T has been eliminated from these data.
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ABCC7 p.Asn1303Lys 15354331:47:194
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PMID: 15358638 [PubMed] Zaman MM et al: "Interleukin 8 secretion from monocytes of subjects heterozygous for the deltaF508 cystic fibrosis transmembrane conductance regulator gene mutation is altered."
No. Sentence Comment
49 Although the majority of CF subjects were homozygous for ⌬F508, mutations on the other allele (compound heterozygotes) included 621 ϩ 1G-T, N1303K, C276X, W1282X, and 1717-1GϾA.
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ABCC7 p.Asn1303Lys 15358638:49:153
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PMID: 15365999 [PubMed] Alper OM et al: "Identification of novel and rare mutations in California Hispanic and African American cystic fibrosis patients."
No. Sentence Comment
14 In a worldwide study of more than 43,000 CF chromosomes, 1652_1654del (c.1520_1522del, p.Phe508del) accounted for 66% of the mutations, while the next four most common mutations 1756G>T(c.1624G>T, p. Gly542Ter), 4041C>G(c.3909C>G, p.Asn1303Lys), 1784G>A(c.1652G>A, p. Gly551Asp), 3978G>A(c.3846G>A, p.Trp1282Ter) had relative frequencies of 1.2-2.4 %.
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ABCC7 p.Asn1303Lys 15365999:14:233
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PMID: 15371902 [PubMed] Watson MS et al: "Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel."
No. Sentence Comment
70 It has been ar- Table 1 CFTR mutation frequency among individuals with clinically diagnosed cystic fibrosis by racial/ethnic group and in a pan-ethnic U.S. population CFTR mutation Mutation frequency among individuals with clinically diagnosed cystic fibrosis (%) Non-Hispanic Caucasian Hispanic Caucasian African American Asian American Ashkenazi Jewish Pan-Ethnic Population5 delF508 72.42 54.38 44.07 38.95 31.41 66.31 G542X 2.28 5.10 1.45 0.00 7.55 2.64 W1282X 1.50 0.63 0.24 0.00 45.92 2.20 G551D 2.25 0.56 1.21 3.15 0.22 1.93 621ϩ1GϾT 1.57 0.26 1.11 0.00 0.00 1.30 N1303K 1.27 1.66 0.35 0.76 2.78 1.27 R553X 0.87 2.81 2.32 0.76 0.00 1.21 dell507 0.88 0.68 1.87 0.00 0.22 0.90 3849ϩ10kbCϾT 0.58 1.57 0.17 5.31 4.77 0.85 3120ϩ1GϾT 0.08 0.16 9.57 0.00 0.10 0.86 R117H 0.70 0.11 0.06 0.00 0.00 0.54 1717-1GϾT 0.48 0.27 0.37 0.00 0.67 0.44 2789ϩ5GϾA 0.48 0.16 0.00 0.00 0.10 0.38 R347P 0.45 0.16 0.06 0.00 0.00 0.36 711ϩ1GϾT 0.43 0.23 0.00 0.00 0.10 0.35 R334W 0.14 1.78 0.49 0.00 0.00 0.37 R560T 0.38 0.00 0.17 0.00 0.00 0.30 R1162X 0.23 0.58 0.66 0.00 0.00 0.30 3569delC 0.34 0.13 0.06 0.00 0.00 0.28 A455E 0.34 0.05 0.00 0.00 0.00 0.26 G85E 0.29 0.23 0.12 0.00 0.00 0.26 2184delA 0.17 0.16 0.05 0.00 0.10 0.15 1898ϩ1GϾA 0.16 0.05 0.06 0.00 0.10 0.13 l148T 0.09 0.09 0.05 0.00 0.10 0.08 1078delT 0.02 0.09 0.00 0.00 0.00 0.03 Total 88.40 71.90 64.51 48.93 94.14 84.00 gued that a laboratory is obligated to report any and all information that is gleaned from a test system, however, there is no regulatory requirement and practice varies.
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ABCC7 p.Asn1303Lys 15371902:70:583
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PMID: 15371903 [PubMed] Sugarman EA et al: "CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations."
No. Sentence Comment
35 87 mutation panel The following mutations were included in the panel: ⌬F508, ⌬F311, ⌬I507, A455E, A559T, C524X, D1152H, D1270N, E60X, G178R, G330X, G480C, G542X, G551D, G85E, G91R, I148T, K710X, L206W, M1101K, N1303K, P574H, Q1238X, Q359K/T360K, Q493X, Q552X, Q890X, R1066C, R1158X, R1162X, R117C, R117H, R1283M, R334W, R347H, R347P, R352Q, R553X, R560T, S1196X, S1251N, S1255X, S364P, S549I, S549N, S549R, T338I, V520F, W1089X, W1282X, Y1092X, Y563D, 1078delT, 1161delC, 1609delCA, 1677delTA, 1717-1GϾA, 1812-1GϾA, 1898ϩ1GϾA, 1898ϩ5GϾT, 1949del84, 2043delG, 2143delT, 2183delAAϾG, 2184delA, 2307insA, 2789ϩ5GϾA, 2869insG, 3120ϩ1GϾA, 3120GϾA, 3659delC, 3662delA, 3791delC, 3821delT, 3849ϩ10kbCϾT, 3849ϩ4AϾG, 3905insT, 394delTT, 405ϩ1GϾA, 405ϩ3AϾC, 444delA, 574delA, 621ϩ1GϾT, 711ϩ1GϾT, 711ϩ5GϾA, 712-1GϾT, 3876delA CFTR mutation analysis Genomic DNA was extracted from peripheral blood lymphocytes, buccal cell swabs, or bloodspots by Qiagen QIAmp 96 DNA Blood Kit. Specimens were tested for 87 mutations by a pooled allele-specific oligonucleotide (ASO) hybridization method as previously described.16,17 Two multiplex chain reactions (PCR) were used to amplify 19 regions of the CFTR gene.
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ABCC7 p.Asn1303Lys 15371903:35:231
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PMID: 15371905 [PubMed] Palomaki GE et al: "Clinical sensitivity of prenatal screening for cystic fibrosis via CFTR carrier testing in a United States panethnic population."
No. Sentence Comment
32 Data from the International Cystic Fibrosis Consortium were taken from Table 1 of its publication.4 Data from the Cystic Fibrosis Foundation National Patient Registry were taken from the year 1999 and stratified according to whether or not the patient was seen Table 1 CFTR mutation frequencies among Hispanic Caucasians with cystic fibrosis within the recommended minimum testing panel Ordera Mutation Mutation frequency (%) CF Consortiumb CF Foundationc Average Cumulative 1 delF508 45.51 63.25 54.38 54.38 2 G542X 5.11 5.09 5.10 59.48 8 delI507 0.59 5.02 2.81 62.29 22 R334W 2.25 1.31 1.78 64.07 6 N1303K 1.65 1.67 1.66 65.73 10 3849 ϩ 10kbC Ͼ T 1.60 1.53 1.57 67.30 7 R553X 0.63 0.73 0.68 67.98 5 W1282X 0.53 0.73 0.63 68.61 19 R1162X 0.57 0.58 0.58 69.19 3 G551D 0.31 0.80 0.56 69.75 12 1717 - 1G Ͼ T 0.10 0.44 0.27 70.02 4 621 ϩ 1G Ͼ T 0.00 0.51 0.26 70.28 14 711 ϩ 1G Ͼ T 0.10 0.36 0.23 70.51 18 G85E 0.10 0.36 0.23 70.74 11 2789 ϩ 5G Ͼ A 0.10 0.22 0.16 70.90 13 R347P 0.10 0.22 0.16 71.06 20 2184delA 0.10 0.22 0.16 71.22 24 3120 ϩ 1G Ͼ T 0.10 0.22 0.16 71.38 17 3569delC 0.10 0.15 0.13 71.51 9 R117H 0.00 0.22 0.11 71.62 23 I148T 0.10 0.07 0.09 71.71 25 1078delT 0.10 0.07 0.09 71.80 16 A455E 0.10 0.00 0.05 71.85 21 1898 ϩ 1G Ͼ A 0.10 0.00 0.05 71.90 15 R560T 0.00 0.00 0.00 71.90 All 25 59.95 83.77 71.90 a The order is based on that found for non-Hispanic Caucasians.3 b Based on between 178 and 958 chromosomes (International Cystic Fibrosis Genetic Analysis Consortium.4 c Based on 1374 chromosomes from clinically diagnosed persons registered in the Cystic Fibrosis Foundation National Patient Registry.
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ABCC7 p.Asn1303Lys 15371905:32:601
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80 The larger data- Table 2 CFTR mutation frequencies among African American individuals with cystic fibrosis within the recommended minimum testing panel Ordera Mutation Mutation frequency (%) CF Consortiumb CF Foundationc Average Cumulative 1 delF508 35.50 52.63 44.07 44.07 24 3120 ϩ 1G Ͼ T 12.50 6.64 9.57 53.64 8 delI507 0.74 3.89 2.32 55.96 7 R553X 2.37 1.37 1.87 57.83 2 G542X 1.18 1.72 1.45 59.28 3 G551D 0.59 1.83 1.21 60.49 4 621 ϩ 1G Ͼ T 1.18 1.03 1.11 61.60 19 R1162X 0.74 0.57 0.66 62.26 22 R334W 0.74 0.23 0.49 62.75 12 1717 - 1G Ͼ T 0.74 0.00 0.37 63.12 6 N1303K 0.00 0.69 0.35 63.47 5 W1282X 0.00 0.47 0.24 63.71 10 3849 ϩ 10kbC Ͼ T 0.00 0.34 0.17 63.88 15 R560T 0.00 0.34 0.17 64.05 18 G85E 0.00 0.23 0.12 64.17 9 R117H 0.00 0.11 0.06 64.23 13 R347P 0.00 0.11 0.06 64.29 17 3569delC 0.00 0.11 0.06 64.35 21 1898 ϩ 1G Ͼ A 0.00 0.11 0.06 64.41 20 2184delA 0.10 0.00 0.05 64.46 23 I148T 0.10 0.00 0.05 64.51 11 2789 ϩ 5G Ͼ A 0.00 0.00 0.00 64.51 14 711 ϩ 1G Ͼ T 0.00 0.00 0.00 64.51 16 A455E 0.00 0.00 0.00 64.51 25 1078delT 0.00 0.00 0.00 64.51 All 25 56.46 72.42 64.51 a The order is based on that found for non-Hispanic Caucasians.3 b Based on between 79 and 169 chromosomes reported by the International Cystic Fibrosis Genetic Analysis Consortium.4 c Based on 874 chromosomes from clinically diagnosed persons registered in the Cystic Fibrosis Foundation National Patient Registry.
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ABCC7 p.Asn1303Lys 15371905:80:598
status: NEW
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107 An earlier article10 reported that 97% of mutations were identified in 90 chromosomes from Ashkenazi Jewish individ- Table 3 CFTR mutation frequencies among Ashkenazi Jewish Caucasian individuals with cystic fibrosis within the recommended minimum testing panel Ordera Mutation Mutation frequency (%) CF Consortiumb Cumulative 5 W1282X 45.92 45.92 1 delF508 31.41 77.33 2 G542X 7.55 84.88 10 3849 ϩ 10kbC Ͼ T 4.77 89.65 6 N1303K 2.78 92.43 12 1717 - 1G Ͼ T 0.67 93.10 7 R553X 0.22 93.32 3 G551D 0.22 93.54 24 3120 ϩ 1G Ͼ T 0.10 93.64 21 1898 ϩ 1G Ͼ A 0.10 93.74 20 2184delA 0.10 93.84 23 I148T 0.10 93.94 11 2789 ϩ 5G Ͼ A 0.10 94.04 14 711 ϩ 1G Ͼ T 0.10 94.14 8 delI507 0.00 94.14 19 R1162X 0.00 94.14 22 R334W 0.00 94.14 4 621 ϩ 1G Ͼ T 0.00 94.14 15 R560T 0.00 94.14 18 G85E 0.00 94.14 9 R117H 0.00 94.14 13 R347P 0.00 94.14 17 3569delC 0.00 94.14 16 A455E 0.00 94.14 25 1078delT 0.00 94.14 Sum 94.14 a The order is based on that found for non-Hispanic Caucasians.3 b Based on between 57 and 503 chromosomes reported by the International Cystic Fibrosis Genetic Analysis Consortium.4 uals with cystic fibrosis, using a panel of 11 mutations.
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ABCC7 p.Asn1303Lys 15371905:107:434
status: NEW
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115 In an- Table 4 CFTR mutation frequencies among Asian American individuals with cystic fibrosis within the recommended minimum testing panel Ordera Mutation Mutation frequency (%) Heim et al.1b CF Foundationc Average Cumulative 1 delF508 18.80 59.09 38.95 38.95 10 3849 ϩ 10kbC Ͼ T 0.00 10.61 5.31 44.26 3 G551D 6.30 0.00 3.15 47.41 6 N1303K 0.00 1.52 0.76 48.17 8 delI507 0.00 1.52 0.76 48.93 2 G542X 0.00 0.00 0.00 48.93 4 621 ϩ 1G Ͼ T 0.00 0.00 0.00 48.93 5 W1282X 0.00 0.00 0.00 48.93 7 R553X 0.00 0.00 0.00 48.93 9 R117H 0.00 0.00 0.00 48.93 11 2789 ϩ 5G Ͼ A 0.00 0.00 0.00 48.93 12 1717 - 1G Ͼ T 0.00 0.00 0.00 48.93 13 R347P 0.00 0.00 0.00 48.93 14 711 ϩ 1G Ͼ T 0.00 0.00 0.00 48.93 15 R560T 0.00 0.00 0.00 48.93 16 A455E 0.00 0.00 0.00 48.93 17 3569delC 0.00 0.00 0.00 48.93 18 G85E 0.00 0.00 0.00 48.93 19 R1162X 0.00 0.00 0.00 48.93 20 2184delA 0.00 0.00 0.00 48.93 21 1898 ϩ 1G Ͼ A 0.00 0.00 0.00 48.93 22 R334W 0.00 0.00 0.00 48.93 23 I148T 0.00 0.00 0.00 48.93 24 3120 ϩ 1G Ͼ T 0.00 0.00 0.00 48.93 25 1078delT 0.00 0.00 0.00 48.93 Sum 25.10 72.74 48.93 a The order is based on that found for non-Hispanic Caucasians.3 b Based on 20 chromosomes.
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ABCC7 p.Asn1303Lys 15371905:115:346
status: NEW
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173 For exam- Table 7 Estimated number of carriers of the 25 recommended CFTR mutations by racial/ethnic group and weighted average, representing the panethnic population in the United States for 2002 Order CFTR mutation Number of CFTR Mutation Carriers Panethnic frequency, % Non-Hispanic Caucasian Hispanic Caucasian African American Asian American Ashkenazi Jewish Total 1 delF508 64,779 8,207 4,272 886 796 78,940 66.31 2 G542X 2,039 770 141 0 191 3,141 2.64 5 W1282X 1,342 95 23 0 1,164 2,624 2.20 3 G551D 2,013 85 117 72 6 2,293 1.93 4 621 ϩ 1G Ͼ T 1,404 39 108 0 0 1,551 1.30 6 N1303K 1,136 251 34 17 70 1,508 1.27 7 R553X 778 424 225 17 0 1,444 1.21 8 delI507 787 103 181 0 6 1,077 0.90 10 3849 ϩ 10kbC Ͼ T 519 237 16 121 121 1,014 0.85 24 3120 ϩ 1G Ͼ T 72 24 928 0 3 1,027 0.86 9 R117H 626 17 6 0 0 649 0.55 12 1717 - 1G Ͼ T 429 41 36 0 17 523 0.44 11 2789 ϩ 5G Ͼ A 429 24 0 0 3 456 0.38 13 R347P 403 24 6 0 0 433 0.36 14 711 ϩ 1G Ͼ T 385 35 0 0 3 423 0.36 22 R334W 125 269 47 0 0 441 0.37 15 R560T 340 0 16 0 0 356 0.30 19 R1162X 206 88 64 0 0 358 0.30 17 3569delC 304 20 6 0 0 330 0.28 16 A455E 304 8 0 0 0 312 0.26 18 G85E 259 35 12 0 0 306 0.26 20 2184delA 152 24 5 0 3 184 0.15 21 1898 ϩ 1G Ͼ A 143 8 6 0 3 160 0.13 23 I148T 80 14 5 0 3 102 0.09 25 1078delT 18 14 0 0 0 32 0.03 All 79,072 10,856 6,193 1,113 2,389 99,684 84.00 Bolded numbers indicate mutations that are more likely to be found in a racial/ethnic group other than non-Hispanic Caucasians.
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ABCC7 p.Asn1303Lys 15371905:173:593
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PMID: 15371906 [PubMed] Kornreich R et al: "Premarital and prenatal screening for cystic fibrosis: experience in the Ashkenazi Jewish population."
No. Sentence Comment
14 Although the demand for screening was great, widespread population screening was not actually recommended by the American College of Obstetrics and Gynecology (ACOG) and American College of Medical Genetics (ACMG) until 2001.5 Based on a frequency of at least 0.1% of mutant alleles in a large CF patient database, a panel of 25 mutations was recommended even though the sensitivity was still below 90% in most ethnic groups.6 The results of screening with this mutation panel were reviewed in 20027 and most recently, in this issue.8 The Ashkenazi Jewish (AJ) population represents a unique group for genetic screening as common mutations occur in prevalent recessive diseases due to founder effect and/or selection.9,10 With regard to CF, five CFTR mutations (W1282X, ⌬F508, G542X, 3849ϩ10kb CϾT, N1303K) account for 97% of the mutant alleles in AJ CF patients.11 This population has a very high acceptance rate for genetic screening and has had a positive experience with carrier screening, beginning with Tay-Sachs disease in 1970.12,13 In this study, we report our experiences with CF carrier screening in the AJ population using two different approaches: premarital (Dor Yeshorim, DY) and prenatal screening (Mount Sinai School of Medicine, MSSM).
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ABCC7 p.Asn1303Lys 15371906:14:818
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19 DOI: 10.1097/01.GIM.0000139510.00644.F7 September/October 2004 ⅐ Vol. 6 ⅐ No. 5 a r t i c l e Genetics IN Medicine Jewish community, began premarital screening in 1983 for Tay-Sachs.14 CF was added to their premarital testing panel in 1993.15 The Genetic Testing Laboratory at MSSM has been conducting prenatal CF carrier screening since 1992 and has performed over 60,000 CF tests.16 Both programs initially screened for five, reported common AJ mutations (W1282X, ⌬F508, G542X, 3849ϩ10kb CϾT, N1303K).11 In 2000, DY observed the presence of the D1152H CF mutation in the AJ population and, therefore, added this mutation along with 1717-1 GϾA to its routine AJ screening panel.
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ABCC7 p.Asn1303Lys 15371906:19:530
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32 For the DY cohort, all individuals were initially tested for five mutations (W1282X, ⌬F508, G542X, 3849ϩ10kb CϾT, N1303K).
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ABCC7 p.Asn1303Lys 15371906:32:133
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36 At MSSM, for the period January 1997 through December 2000 for which data and ethnic information are available, five mutations (W1282X, ⌬F508, G542X, 3849ϩ10kb CϾT, N1303K) were analyzed by PCR amplification and restriction enzyme analyses.
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ABCC7 p.Asn1303Lys 15371906:36:184
status: NEW
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45 The G542X, 3849ϩ10 kb CϾT, and N1303K were tested in over 117,000 screenees and occurred at similar frequencies in both programs, with overall detection rates of 1 in 413 (0.0024), 1 in 490 (0.0020), and 1 in 633 (0.0016), respectively.
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ABCC7 p.Asn1303Lys 15371906:45:43
status: NEW
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47 For the five mutations (W1282X, ⌬F508, G542X, 3849ϩ10kb CϾT, N1303K) for which over 117,000 AJ screenees were tested, a total of 4,498 carriers were identified (1 in 26 or 0.038).
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ABCC7 p.Asn1303Lys 15371906:47:80
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68 Of the remaining 31 prenatal diagnoses, 24 fetuses were heterozygotes and Table 1 Carrier frequencies of seven routinely tested AJ CF mutations CF mutation No. individuals tested Frequency Combined frequency Previous studies DY MSSM DY MSSM Ref 3 n ϭ 6076 Ref 15 n ϭ 6850 W1282X 110889 6247 1 in 49.7 (0.0201) 1 in 48.8 (0.0205) 1 in 49.6 (0.0202) 1 in 48.2 (0.0207) 1 in 48.2 (0.0207) ⌬F508 110898 6247 1 in 81.7 (0.0122) 1 in 86.8 (0.0115) 1 in 82.0 (0.0122) 1 in 79.7 (0.0126) 1 in 77.9 (0.0128) D1152H 42208 2322 1 in 189.2 (0.00528) 1 in 193.5 (0.00517) 1 in 189.5 (0.00528) 1 in 113.5a (0.00881) NDb G542X 110893 6247 1 in 410.7 (0.00243) 1 in 446.2 (0.00224) 1 in 412.5 (0.00242) 1 in 338.3 (0.00296) 1 in 506.3 (0.00197) 3849ϩ10kb CϾT 110888 6247 1 in 490.7 (0.00204) 1 in 480.5 (0.00208) 1 in 490.1 (0.00204) 1 in 402.9 (0.00248) 1 in 607.6 (0.00165) N1303K 110894 6247 1 in 637.2 (0.00157) 1 in 567.9 (0.00176) 1 in 633.2 (0.00158) 1 in 913.3 (0.00109) 1 in 552.4 (0.00181) 1717-1 GϾA 57869 2322 1 in 7233.6 (0.000138) 1 in 2322 (0.000431) 1 in 6687.9 (0.000150) NDb NDb Five mutations (Without D1152H and 1717-1 GϾA) 1 in 26.1 (0.0384) 1 in 26.2 (0.0381) 1 in 26.1 (0.0384) 1 in 25.1 (0.0398) 1 in 25.7 (0.0389) Seven mutations 1 in 22.8 (0.0438) 1 in 22.9 (0.0437) 1 in 22.8 (0.0438) a n ϭ 1305. b Not determined.
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ABCC7 p.Asn1303Lys 15371906:68:891
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69 Table 2 Distribution of CF mutations in DY and MSSM carriers for five and seven common AJ mutations CF mutation % of AJ carriers (5 mutations) % of AJ carriers (7 mutations) DY MSSM Combined DY MSSM Combined W1282X 52.3 53.8 53.1 45.9 46.9 46.4 ⌬F508 31.9 30.2 31.0 27.9 26.3 27.1 G542X 6.3 5.9 6.1 5.5 5.1 5.3 3849ϩ10kb CϾT 5.3 5.5 5.4 4.7 4.8 4.8 N1303K 4.1 4.6 4.4 3.6 4.0 3.8 D1152H - - - 12.1 11.8 12.0 1717-1GϾA - - - 0.3 1.0 0.6 seven did not carry either parental mutation.
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ABCC7 p.Asn1303Lys 15371906:69:368
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83 Previous studies of AJ patients with CF indicated that screening for five mutations (W1282X, ⌬F508, G542X, 3849ϩ10kb CϾT, N1303K) would detect 97% of alleles causing CF in the AJ population.11 Based on the data presented in this study, the largest dataset on AJ carrier screening reported to date, the CF carrier frequency in the 100% AJ population is about 1 in 26 for these five mutations (Table 1).
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ABCC7 p.Asn1303Lys 15371906:83:141
status: NEW
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86 For example, W1282X was the most prevalent mutation among Ashkenazi Jews, present in 46.4% of AJ carriers, whereas it was present in only 1.5% of non-Hispanic Caucasian CF patients.8 ⌬F508, the most common mutation in non-Hispanic Caucasian CF pa- Table 3 Frequency of CFTR mutations among screenees reporting 100% AJ or Ͻ 100% AJ descent who requested carrier testing for CF and at least one other AJ recessive disease CF mutation % of mutations in carriers reporting 100% AJ descent (n ϭ 45,530-117,145) % of mutations among carriers reporting Ͻ100% AJ descent (n ϭ 7,393) % of Non-Hispanic Caucasian CF patient chromosomes8 (n ϭ 37,263) W1282X 46.4 (n ϭ 117,136) 32.3 1.5 ⌬F508 27.1 (n ϭ 117,145) 35.7 71.5 D1152H 12.0 (n ϭ 44,530) 8.7 0.03 G542X 5.3 (n ϭ 117,140) 6.1 2.3 3849ϩ10kb CϾT 4.8 (n ϭ 117,135) 4.9 0.7 N1303K 3.8 (n ϭ 117,141) 3.0 1.3 1717-1GϾA 0.6 (n ϭ 60,191) 1.9 0.7 R117H a 2.7 0.8 I148T a 2.3 0.05 R334W - 0.76 0.16 A455E - 0.76 0.19 G551D a 0.38 2.5 R553X - 0.38 1.0 a These mutations were detected when screening Ϸ2,300 100% AJ individuals with the ACMG recommended panel.
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ABCC7 p.Asn1303Lys 15371906:86:902
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104 Based on the results of these studies, it is recommended that premarital/prenatal carrier screening for CF be performed by testing the five common AJ CFTR mutations (W1282X, DF508, G542X, 3849ϩ10kb CϾT, N1303K), along with D1152H, for individuals who report that they are 100% AJ.
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ABCC7 p.Asn1303Lys 15371906:104:215
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PMID: 15371908 [PubMed] Buyse IM et al: "Use of MALDI-TOF mass spectrometry in a 51-mutation test for cystic fibrosis: evidence that 3199del6 is a disease-causing mutation."
No. Sentence Comment
77 This assay also demonstrated heterozygosity for the G542X mutation, and reflex testing for the 5T variant at CFTR intron 8 showed a genotype of 7T/9T in this patient (data not Table 3 Description of the 16 multiplex assays designed to analyze 51 CFTR mutations Multiplex Mutations Exon 1 1078delT, G314E, R352Q, G330X 7 2 R347H, R347P, R334W, 1717-1A 7, 11 3 R553X, S549N, R1162X 11, 19 4 A559T, R560T, G551D 11 5 G542X, S549R, 621ϩ1T, Y122X 4, 11 6 W1282X, 3876delA, 3905insT, D1152H 18, 20 7 3849ϩ4G, 3659delC, 1898ϩ1A 12, 19 8 405ϩ1A, 405ϩ3C, 3120A, 3120ϩ1A 3, 16 9 394delTT, E60X, G85E 3 10 A455E, ⌬F508a 9, 10 11 G480C, Q493X, V520F 10 12 711ϩ1T, G178R, 3199del6 5, 17a 13 2143delT, 2184delA, K710X, F316L 7, 13 14 I148T, R117H, R117C 4 15 N1303K, 2789ϩ5A, 3849ϩ10kbT 14b, intron19, 21 16 ⌬I507a 10 17 5Tb intron 8 a F508C and I507V, I506V, I506M variants are tested for concurrently with the ⌬F508 and ⌬I507 assays respectively.
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ABCC7 p.Asn1303Lys 15371908:77:794
status: NEW
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PMID: 15371909 [PubMed] Edelmann L et al: "Cystic fibrosis carrier screening: validation of a novel method using BeadChip technology."
No. Sentence Comment
35 Mutation controls included DNA from previously identified positive patient samples (I148T, D1152H, W1282X, R117H, G85E, A455E, delF508, N1303K) and DNA from NIGMS Human Genetic Cell Repositories (Coriell Cell Repositories) (delF508, delI507, G542X, R560T, 3849ϩ10kbCϾT, N1303K, G85E; G551D, R553X, 621ϩ1GϾT, 1717-1GϾA, A455E, R334W, R347P, R1162X, 3659delC; 711ϩ1GϾT, 2789ϩ5GϾA, 3120ϩ1GϾA).
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ABCC7 p.Asn1303Lys 15371909:35:136
status: NEW
X
ABCC7 p.Asn1303Lys 15371909:35:282
status: NEW
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46 Mutant ASOs were end-labeled with ␥-32 P-ATP and pooled into three subgroups (IA-IC) for Group I and four subgroups (IIA-IID) for Group II mutations with the following breakdown of mutations: IA: delF508, delI507, W1282X, R117H; IB: G542X, R560T, 3849ϩ10kbCϾT, N1303K, G85E; IC: G551D, R553X, 621ϩ1GϾT, 1717-1GϾA, I148T; IIA: A455E, R334W, D1152H; IIB: R347P, 1078delT, R1162X, 3659delC; IIC: 711ϩ1GϾT, 1898ϩ1GϾA, 2789ϩ5GϾA, 3120ϩ1GϾA; IID: 2184delA.
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ABCC7 p.Asn1303Lys 15371909:46:280
status: NEW
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160 I II III IV V VI VII VIII Totals Samples tested 87 57 69 72 66 35 72 61 519 Controls testedk 0h 17h 20 29 22 16 20 21 145 PCR Failuresi 4 4 2 1 1 2 1 3 18 (3.5%) Assay Failuresi 2 0 1 0 2 2 1 1 9 (1.7%) Positives 4a 3b 0 3c 4d 2e 2f 1g 19 (3.7%) a W1282X, delF508, D1152H, W1282X b delF508, delF508, D1152H c delF508, R117H, R117H d G542X, delF508, D1152H, N1303K (does not include proficiency samplesj ) e W1282X, delF508 f I148T, 3849ϩ10kbCϾT g I148T h Runs I and II were amplified with the same master mix and used the same control samples.
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ABCC7 p.Asn1303Lys 15371909:160:357
status: NEW
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PMID: 15379964 [PubMed] Cuppens H et al: "CFTR mutations and polymorphisms in male infertility."
No. Sentence Comment
34 Examples include the G542X, G551D, R553X, W1282X and N1303K mutations.
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ABCC7 p.Asn1303Lys 15379964:34:53
status: NEW
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PMID: 15520400 [PubMed] Niel F et al: "Rapid detection of CFTR gene rearrangements impacts on genetic counselling in cystic fibrosis."
No. Sentence Comment
136 The subjects were divided into three groups according to the results of a previous screening: (i) 43 CF patients who fulfilled the diagnostic criteria of CF15 and who carried a CF mutation, and seven parents of deceased CF patients, a CF mutation having already been identified in the other parent (50 unidentified CF alleles); (ii) 12 CF patients with no identified CF mutation (24 unidentified CF alleles); and (iii) 16 patients apparently homozygous for a CFTR mutation and who had CF (F508del 2n = 6-, 2104insA22109del10, S945L, 3120+1GRA, N1303K) or a CFTR related disease, that is, isolated CBAVD (D110H, R117H, L997F, R74W-D1270N) or DB (R334W, R668C- G576A-D443Y) (0-16 unidentified CF alleles).
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ABCC7 p.Asn1303Lys 15520400:136:544
status: NEW
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PMID: 15528020 [PubMed] Cohn JA et al: "The role of cystic fibrosis gene mutations in determining susceptibility to chronic pancreatitis."
No. Sentence Comment
78 The European data Table 1 Abnormal CFTR and PSTI genotypes detected in two studies of idiopathic chronic pancreatitis* CFTR genotype category N Genotypes detected in individual subjects US study (Noone et al [47]) CFsev / CFm-v compound heterozygotes 8 DF508 / R117H-7T**; DF508 / 5T; DF508 / 5T; DF508 / D1152H; DF508 / D1152H; DF508 / P574H; DF508 / 3120G>A; 621þ1G>T/G1069R CFm-v / CFm-v compound heterozygotes 1 5T / 5T** CFsev / - (CF carriers) 1 N1303K / - CFm-v / - 7 R117H-7T / -; 5T / -**; 5T / -; 5T / -; 5T / -; 5T / -; 5T / - Normal (- / -) CFTR genotype 22 1 was homozygous for the N34S PSTI mutation; 5 were N34S carriers European study (Audrezet et al [50]) CFsev / CFm-v compound heterozygotes 4 DF508/R352Q; DF508/P5L; DF508/Q1476X; W1282X/5T*** CFm-v / CFm-v compound heterozygotes 2 V562I/5T; E217G/A1136T CFsev / - (CF carriers)**** 3 DF508 / -; DF508 / -; G542X / - CFm-v / - 9 L967S/-**; IVS18-20T>C/-**; c.4575þ2G>A/-; IVS3-6T>C; 5T/-; 5T/-; 5T/-; 5T/-; 5T/- Normal (- / -) CFTR genotype 17 1 was homozygous for the N34S PSTI mutation; 1 was a N34S carrier * CFTR mutations were classified as causing either severe (CFsev ) or mild-variable loss-of-function (CFm-v ) [18,47]; all detected CFsev mutations are CF-causing mutations according to current consensus criteria [79].
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ABCC7 p.Asn1303Lys 15528020:78:457
status: NEW
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82 **** A fourth patient had N1303K / - (CFTR), but was not available for further testing.
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ABCC7 p.Asn1303Lys 15528020:82:26
status: NEW
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PMID: 15536480 [PubMed] Modiano G et al: "A large-scale study of the random variability of a coding sequence: a study on the CFTR gene."
No. Sentence Comment
33 In the Tajima`s test,19 the null hypothesis of neutrality is rejected if a statistically significant difference between p Common and rare nonsynonymous and synonymous cSNSs G Modiano et al European Journal of Human Genetics Table 1 List of the 61 cSNSsa encountered in the present survey The random samples of genes (and the technique utilized) cSNS variants found NE Italy (DGGE) Central Italy (DGGE) Southern France (DGGE) Northern France (DHPLC) Spain (SSCA) Czechia (DGGE) Hb  104 Exon Exon Length (bp) Ref. no. SNS SASc 1st 100d 2nd 500 1st 100d 2nde 1st 100d 2nd 500 1st 100 2nde 82d 72 Abs. Freq. Total sample size q  104 se  104 NSf Sf 1g 53 0 0 0 0 0/452 0 924 2 111 1 223C4T R31C 1 1 1/500 1 1 0 0/450 0 5 (11) 1 932 (2 432) 45.23 13.61 90 2 224G4T R31L 0 0 0/500 0 0 0 1/450 0 1 1 932 5.17 5.17 10 3 257C4T S42F 0 0 1/500 0 0 0 0/450 0 1 1 932 5.17 5.17 10 3 109 4 334A4G K68E 1 0 0 0/498 0 0 0 0/452 0 0 1 2 504 3.99 3.99 8 5 352C4T R74W 0 0 0 0/498 0 0 0 1/452 0 0 1 2 504 3.99 3.99 8 6 356G4A R75Q 1 7 1 7/498 2 9 2 9/452 0 2 40 (40) 2 504 (2 544) 157.23 24.66 310 7 386G4A G85E 0 0 1 1/498 0 0 0 0/452 0 0 2 2 504 7.99 5.65 16 4 216 8 482G4A R117H 0 0 0 0/292 0 2 0 1/456 0 0 3 2 302 13.03 7.52 26 9 528T4G I132M 0 0 0 0/292 0 0 0 1/456 0 0 1 2 302 4.34 4.34 8 10 575T4C I148T 1 2 0 1/292 0 0 0 1/456 0 1 6 2 302 26.06 10.63 52 5 90 11 640C4T R170C 0 0 0 0/6 0 0 1/448 0 1 1 436 6.96 6.96 14 12 641G4A R170H 1 1 0 0/6 0 0 2/448 0 4 (4) 1 436 (1 930) 20.73 10.35 41 6a 164 0 0 0/6 0 0 0/432 0 0 992 6b 126 0 0 0/6 0 0 0/454 0 942 7 247 0 0 0/6 0 0 0/796 0 1 284 8 93 13 1281G4A L383 0 0 0 0/6 0 0 1/456 0 0 1 1 516 6.60 6.60 13 9 183 14 1402G4A G424S 0 0 0/6 0 0 1/454 0 1 940 10.64 10.64 21 15 1459G4T D443Y 0 0 0/6 0 0 1/454 0 1 940 10.64 10.64 21 10 192 16 1540A4G M470Vh 42 197 30 37/96 39 199 (i) (i) 27 571(736) 1 484 (1 912) 3849.37 111.28 4 735 17 1598C4A S489X 0 0 0 0/96 0 0 0 1/796 0 1 2 374 4.21 4.21 8 18 1648A4G I506V 1 0 0 0/96 0 0 0 0/796 0 1 2 374 4.21 4.21 8 19 1655T4G F508C 0 1 0 0/96 0 0 0 1/796 0 2 2 038 8.42 5.96 17 20 1716G4A Q528 2 16 1 0/96 0 19 i I 5 43 (58) 1 478 (2 024) 286.56 37.08 557 11 95 21 1756G4T G542X 0 2 0 0/134 0 0 0/796 0 0 2 1 984 10.08 7.12 20 22 1764T4G G544 0 0 0 0/134 0 0 1/796 0 0 1 1 984 5.04 5.04 10 23 1784G4A G551D 0 0 0 0/134 0 0 1/796 0 0 1 1 984 5.04 5.04 10 12 87 24 1816G4A V562I 0 0 0 0 1 0 0/450 0 0 1 (1) 2 004 (2 504) 3.99 3.99 8 25 1816G4C V562L 0 0 0 1 0 0 1/450 0 0 2 (3) 2 004 (2 504) 11.98 6.91 24 26 1859G4C G576A 1 2 0 1 11 0 8/450 0 0 23 (27) 2 004 (2 538) 106.38 20.36 213 13 724j 449 27 1997G4A G622D 0 0 0/80 0/96 1 0 0 0/444 0 1 2 002 5.00 5.00 10 28 2082C4T F650 1 0 0/80 0/20 0 0 0 0/444 0 1 (1) 1 926 (2 412) 4.15 4.15 8 29 2134C4T R668C 1 2 0/80 0/96 1 11 0 12/444 0 27(32) 2 002 (2 558) 125.10 21.98 247 275 30 2377C4T L748 0 0 0/6 0 1 1 388 25.77 25.77 52 14a 129 31 2670G4A W846X 0 0 0/6 0 1 0/452 0/80 0 1 1 010 9.90 9.90 20 32 2694T4G T854 33 23 0/6 33 38 149/452 14/80 11 301 1 010 2980.20 143.92 4 184 33 2695G4A V855I 0 0 0/6 0 0 1/452 0/80 0 1 1 010 9.90 9.90 20 14b 38 0 0 0 0/520 0 0 0 0/446 0 2 448 15 251 34 2816G4C S895T 0 0 0/6 0 0 2/436 0 0 2 996 20.08 14.18 40 35 2831A4C N900T 0 0 0/6 0 0 1/436 0 0 1 996 10.04 10.04 20 36 2988G4C M952I 0 0 0/6 0 0 1/436 0 0 1 996 10.04 10.04 20 37 3030G4A T966 (2)k (1)k 0 6/436 0 6 (25)k 618 (1814)k 137.82 27.37 272 38 3032T4C L967S 0 0 0/6 0 0 1/436 0 0 1 996 10.04 10.04 20 16 80 0 0 0/498 0 0 0/450 0 0 1 502 17a 151 39 3123G4C L997F 0 2 2 1/494 0 7 1 4/454 0 0 17 2 502 67.95 16.42 135 40 3157G4A A1009T 0 2 0 0/494 0 0 0 0/454 0 0 2 2 502 7.99 5.65 16 41 3212T4C I1027T 1 0 0 0/494 0 0 0 0/454 0 0 1 2 502 4.00 4.00 8 17b 228 42 3286T4G F1052V 1 1 0 1/194 0 0 0 0/452 0 0 3 (3) 2 200 (2 240) 13.39 7.73 27 43 3337G4A G1069R 0 1 0 0/194 0 0 0 0/452 0 0 1 2 200 4.55 4.55 9 CommonandrarenonsynonymousandsynonymouscSNSs GModianoetal 186 EuropeanJournalofHumanGenetics 44 3345G4T Q1071H 0 0 0 0/194 0 1 0 0/452 0 0 1 2 200 4.55 4.55 9 45 3417A4T T1995 1 3 0 0/194 1 1 0 0/452 0 0 6 (8) 2 200 (2 506) 31.92 11.27 64 46 3419T4G L1096R 0 0 0 0/194 1 0 0 0/452 0 0 1 2 200 4.55 4.55 9 47 3477C4A T1115 0 0 0 0/194 0 0 0 1/452 0 0 1 2 200 4.55 4.55 9 18 101 48 3523A4G I1131V 0 0 1 0/10 0 0 0/448 0 0 1 (2) 1 512 (1 908) 10.48 7.07 21 49 3586G4C D1152H 0 0 0 0/10 0 0 1/448 0 0 1 1 512 6.61 6.61 13 19 249 50 3617G4T R1162L 0 0 1 1/494 0 0/260 0 0/454 0 0 2 2 262 8.84 6.25 18 51 3690A4G Q1186 0 0 0 0/494 0 0/260 0 0/454 1 0 1 2 262 4.42 4.42 9 52 3813A4G L1227 0 1 0 0/494 0 0/260 0 0/454 0 0 1 2 262 4.42 4.42 9 53 3837T4G S1235R 1 1 0 1/494 0 4/260 0 7/454 0 1 15 (15) 2 262 (2 310) 69.94 16.71 140 20 156 54 4002A4G P1290 2 3 0/6 3 5 18/454 3/80 2 36 1 012 357.73 58.22 690 21 90 55 4009G4A V1293I 0 0 0/6 0 0/300 0 1/456 0 0 1 1 316 7.60 7.60 15 56 4029A4G T1299 1 0 0/6 0 1/300 0 1/456 0 0 3 (8) 1 316 (2 330) 34.33 12.12 69 57 4041C4G N1303K 1 0 0/6 0 0/300 0 0/456 0 0 1 1 316 7.60 7.60 15 58 4085T4C V1318A 0 0 0/6 0 0/300 0 1/456 0 0 1 1 316 7.60 7.60 15 22 173 0 0 0/18 0 0 0/450 0 0 1 022 23 106 0 0 0 0/6 0 0 0/448 0 1 436 24l 198+3 59 4404C4T Y1424 1 0 0/6 1 2 5/420 0 2 11 (32) 980 (2 516) 127.19 22.34 251 60m 4521G4A Q1463 (21) (16) (3/32) (14/80) (30) (94/420) 15/76 (17) 15 (227) 76 (1052) 2142.86 131.07 3 367 61 4563T4C D1477 0 0 0/6 0 1 0/420 0 0 1 980 10.20 10.20 20 Totals 6 525 9 584 16 109 The bracketed figures include also the RFLP analysis data (see Materials and methods); the NE Italy, Central Italy, Southern and Northern France are each subdivided into two samples where the 1st is made up of 100 genes.
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ABCC7 p.Asn1303Lys 15536480:33:4908
status: NEW
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PMID: 15537723 [PubMed] Jalalirad M et al: "First study of CF mutations in the CFTR gene of Iranian patients: detection of DeltaF508, G542X, W1282X, A120T, R117H, and R347H mutations."
No. Sentence Comment
15 Most of the families in whom ∆F508, W1282X, and G542X mutations BRIEF REPORTS Journal of Tropical Pediatrics Vol. 50, No.
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ABCC7 p.Asn1303Lys 15537723:15:653
status: NEW
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16 6 359 First Study of CF Mutations in the CFTR Gene of Iranian Patients: Detection of ∆F508, G542X, W1282X, A120T, R117H, and R347H Mutations by M. Jalalirad,a,b M. Houshmand,a R. Mirfakhraie,a M. H. Goharbari,a and F. Mirzajania a National Research Center for Genetic Engineering and Biotechnology (NRCGEB),Tehran, Iran b Biology Department, Gilan University, Rasht, Iran Summary Thirty-seven unrelated Iranian CF families were screened for the presence of seven common mutations (∆F508, G542X, W1282X, G551D, N1303K, 1717-1G→A, and 621-1G→T) using ARMS PCR and exons 4 and 7 of the CFTR gene by SSCP method.
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ABCC7 p.Asn1303Lys 15537723:16:524
status: NEW
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PMID: 15614862 [PubMed] D'Apice MR et al: "Segregation analysis in cystic fibrosis at-risk family demonstrates that the M348K CFTR mutation is a rare innocuous polymorphism."
No. Sentence Comment
3 We investigate whether the (paternal) M348K mutation is a benign polymorphism or a disease-causing mutation in a patient clinically affected with CF, with the second (maternal) CFTR allele identified as N1303K.
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ABCC7 p.Asn1303Lys 15614862:3:203
status: NEW
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28 Received: 30 April 2004 Revised: 7 October 2004 Accepted: 10 October 2004 M. R. D`APICE ET AL. 1 1 1 1 3 4 1 2 1 1 4 1 1 2 1 1 4 1 1 2 1 1 2 1I:1 II:1 II:2 I:2 G1244E M348K G1244E N1303K N1303K G1244E N1303K IVS8GT IVS17bCA IVS17bTA IVS8GT IVS17bCA IVS17bTA IVS8GT IVS17bCA IVS17bTA IVS8GT IVS17bCA IVS17bTA Figure 1-The reported family pedigree.
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ABCC7 p.Asn1303Lys 15614862:28:182
status: NEW
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ABCC7 p.Asn1303Lys 15614862:28:189
status: NEW
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ABCC7 p.Asn1303Lys 15614862:28:203
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29 The proband (II:1) and the fetus (II:2) have each inherited G1244E and N1303K.
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ABCC7 p.Asn1303Lys 15614862:29:71
status: NEW
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30 Their asymptomatic father (I:1) shows the G1244E CF mutation and the M348K polymorphism; their mother (I:2) shows the N1303K mutation.
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ABCC7 p.Asn1303Lys 15614862:30:118
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34 The N1303K mutation was identified, and shown to be inherited from the mother (Figure 1).
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ABCC7 p.Asn1303Lys 15614862:34:4
status: NEW
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38 Direct analysis of exons 7 and 20 showed that the patient received only the G1244E paternal mutation and the N1303K maternal mutation giving a genotype N1303K/G1244E.
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ABCC7 p.Asn1303Lys 15614862:38:109
status: NEW
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ABCC7 p.Asn1303Lys 15614862:38:152
status: NEW
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39 Analysis using three intragenic microsatellites (IVS8GT, IVS17bTA, IVS17bCA) confirmed that the affected proband inherited the paternal chromosome carrying the G1244E mutation and N1303K from his mother.
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ABCC7 p.Asn1303Lys 15614862:39:180
status: NEW
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51 The fetus (II-2, Figure 1) was compound heterozygous for the N1303K/G1244E mutations and haploidentical to the affected proband.
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ABCC7 p.Asn1303Lys 15614862:51:61
status: NEW
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PMID: 15618584 [PubMed] Dormer RL et al: "Sildenafil (Viagra) corrects DeltaF508-CFTR location in nasal epithelial cells from patients with cystic fibrosis."
No. Sentence Comment
257 The only other report of altered trafficking of CFTR with a mutation in NBD2 is N1303K.15 The present results, showing that sildenafil corrects DF508- and R1283M-CFTR location, both mutations in nucleotide binding domains, will provide insights into the mechanism of action of drugs that increase CFTR trafficking.
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ABCC7 p.Asn1303Lys 15618584:257:80
status: NEW
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PMID: 15638824 [PubMed] Castaldo G et al: "Comprehensive cystic fibrosis mutation epidemiology and haplotype characterization in a southern Italian population."
No. Sentence Comment
33 The 13 mutations in this panel are: F508del, N1303K, G542X, W1282X, 2183AA>G, 1717-1G>A, R553X, I148T, R1158X, 711+1G>T, 4016insT, L1065P and G1244E.
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ABCC7 p.Asn1303Lys 15638824:33:45
status: NEW
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52 We also identified three homozygotes for G542X, three for 852del22, two for 2183AA>G, and one each for N1303K, 1717-1G>A, 4016insT, R553X, R1158X and L1065P.
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ABCC7 p.Asn1303Lys 15638824:52:103
status: NEW
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62 A procedure for the large-scale analysis of several mutations peculiar to southern Italy is also indicated Mutation Analytical CF alleles Campania Basilicata Puglia Total procedure n = 340 n = 52 n = 350 n = 742 DF508 55.6 55.8 46.8 51.5 N1303K 7.3 3.8 7.7 7.3 G542X 5.0 3.8 7.1 5.9 W1282X 3.5 3.8 0.6 2.2 2183 AA>G 2.3 5.8 0.8 1.9 852del22 0 5.8 3.2 1.9 3% agarose 1717-1G>A 2.3 1.9 1.1 1.8 4382delA 0 0 3.7 1.8 RE (Ear I -) 1259insA 0 0 3.1 1.5 4016insT 2.1 0 1.1 1.5 ASO R553X 1.5 0 1.7 1.5 R1158X 1.5 0 1.3 1.2 ASO or RE (Sfa N 1 -) L1077P 0.6 0 1.9 1.2 I502T 0.3 0 2.0 1.1 RE (Mse I -) 3849+10kbC>T 0 1.9 1.6 0.9 D579G 0 0 1.6 0.8 RE (Avr II +) G1244E 0.9 3.8 0.3 0.8 ASO or RE (Mbo II +) G1349D 0 0 1.7 0.8 RE (Sty I -) 2789+5 G>A 0.6 0 0.8 0.7 711+1 G>T 1.5 0 0 0.7 ASO L1065P 1.2 0 0 0.5 ASO or RE (Mnl I +) R347P 0.3 0 0.9 0.5 2522insC 0.9 0 0 0.4 E585X 0.6 0 0 0.3 G85E 0.6 0 0 0.3 G178R 0.6 0 0 0.3 D1152H 0.3 0 0.3 0.3 I148T-3195del6 0.6 0 0 0.3 I148T (alone) 0 0 0.3 0.1 R334W 0 0 0.3 0.1 DI507 0 0 0.3 0.1 I1005R 0 0 0.3 0.1 3272-26A>G 0.3 0 0 0.1 2711delT 0.3 0 0 0.1 L558S 0 1.9 0 0.1 W1063X 0 0 0.3 0.1 D110H 0.3 0 0 0.1 S549R (A>C) 0 1.9 0 0.1 2184insA 0.3 0 0 0.1 3131del22 0.3 0 0 0.1 R709N 0 0 0.3 0.1 A349V 0 0 0.3 0.1 4015insA 0 0 0.3 0.1 Y849X 0 1.9 0 0.1 Cumulative 91.6 92.1 91.7 91.5 Unknown 8.4 7.9 8.3 8.5 Total 100,0 100,0 100,0 100,0 RE: restriction enzyme (-/+: abolition or introduction of a RE site); ASO: allele specific oligonucleotide Figure 2 Multiplex denaturing gradient gel electrophoretic analysis of exons 8, 5 and 18 of the cystic fibrosis transmembrane regulator gene in a cystic fibrosis patient (case n.
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ABCC7 p.Asn1303Lys 15638824:62:238
status: NEW
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PMID: 15644056 [PubMed] Mennicke K et al: "Rational approach to genetic testing of cystic fibrosis (CF) in infertile men."
No. Sentence Comment
49 In the presence of CFTR mutations, further genetic screening for the seven most frequently identified CF mutations [G542X, N1303K, 1717-1(GoA), W1282X, G551D, R553X, DI507; The Cystic Fibrosis Analysis Consortium, 1990] was performed.
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ABCC7 p.Asn1303Lys 15644056:49:123
status: NEW
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PMID: 15672947 [PubMed] Augarten A et al: "Systemic inflammatory mediators and cystic fibrosis genotype."
No. Sentence Comment
5 Group A included 25 patients who carried two mutations associated with a pathological sweat test and pancreatic insufficiency (∆F508, W1282X, G542X, N1303K, S549R).
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ABCC7 p.Asn1303Lys 15672947:5:156
status: NEW
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28 Group A included 25 patients who carried two mutations associated with a pathological sweat test and pancreatic insufficiency (∆F508, W1282X, G542X, N1303K, S549R) [2].
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ABCC7 p.Asn1303Lys 15672947:28:156
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67 : Systemic inflammatory mediators and cystic fibrosis genotype 101 Table 1 Clinical characteristics of cystic fibrosis (CF) patients Group Aa (n=25) Group Bb (n=11) P Age (years) 16.9±7.2 17.7±9.1 NS Pancreatic sufficiency 0% 0/25 36.3% 4/11 <0.01 Sweat chloride (mmol/l) 105±28 92±18.6 NS Weight percentiles 19±19.8 57.2±25.2 <0.01 Sputum Pseudomonas 88% 22/24 40% 4/10 <0.01 a Group A CF patients carrying two mutations associated with severe disease presentation (∆F508, W1282X, G542X, N1303K, S549R) b Group B CF patients carrying mutations associated with mild disease presentation (3849+10kb CǞT, 5T) Table 2 Comparison of serum chemokine levels between groups (IL-8 interleukin-8, MCPI monocyte chemoattractant protein-1) Chemokine Group Aa Group Bb P IL-8 (pg/ml) 11.4±2.1 5.0±0.9 0.01 MCP1(pg/ml) 157±16 88.8+16.4 0.01 RANTES (pg/ml) 323±48 287.5±93 NS a Group A CF patients carrying two mutations associated with severe disease presentation (∆F508, W1282X, G542X, N1303K, S549R) b Group B CF patients carrying mutations associated with mild disease presentation (3849+10kb CÞT, 5T) Fig. 1 Relationship between interleukin-8 (IL-8) levels and forced expiratory volume in 1 s (FEV1) values defective protein production; class II, defective protein processing; class III, defective chloride channel regulation; and class IV, defective chloride channel conduction.
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ABCC7 p.Asn1303Lys 15672947:67:526
status: NEW
X
ABCC7 p.Asn1303Lys 15672947:67:1049
status: NEW
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PMID: 15684079 [PubMed] Randak CO et al: "ADP inhibits function of the ABC transporter cystic fibrosis transmembrane conductance regulator via its adenylate kinase activity."
No. Sentence Comment
32 In contrast, the N1303K mutation is predicted to lie outside the ATP-binding site.
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ABCC7 p.Asn1303Lys 15684079:32:17
status: NEW
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PMID: 15699697 [PubMed] Walkowiak J et al: "Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations."
No. Sentence Comment
47 RESULTS Among 28 genotyped CF infants, the following allele mutations were found: 51 DF508, four CFTRdele2,3(21kB) and one N1303K.
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ABCC7 p.Asn1303Lys 15699697:47:123
status: NEW
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PMID: 15704202 [PubMed] Massie J et al: "Diagnosis of cystic fibrosis after newborn screening: the Australasian experience--twenty years and five million babies later: a consensus statement from the Australasian Paediatric Respiratory Group."
No. Sentence Comment
49 T, R553X, N1303K, and R117H; New Zealand, DF508, G551D, and G542X.
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ABCC7 p.Asn1303Lys 15704202:49:10
status: NEW
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PMID: 15705796 [PubMed] O'Sullivan BP et al: "Platelet activation in cystic fibrosis."
No. Sentence Comment
44 Clinical characteristics of cystic fibrosis patients Patient Age, y Vitamin E, mg/L* FEV1, % predicted† Inpatient or outpatient‡ Genotype Platelet studies§ 1 20 6.6 25 In ␦F508/unk A 2 20 3.6 70 In ␦F508/G542X A 3 11 16.8 92 Out ␦F508/dF508 A 4 16 5.4 101 Out ␦F508/G542X A 5 9 3.9 124 Out ␦F508/dF508 A,F 6 6 5.1 118 Out ␦F508/dF508 A,F 7 13 8.1 119 Out ␦F508/dF508 A,F 8 10 9.7 104 Out ␦F508/dF508 A,F 9 22 9.0 58 In ␦F508/dF508 A 10 19 8.0 57 Out ␦F508/N1303K A 11 17 7.0 24 Out ␦F508/dF508 A,D,E 12 20 3.2 55 Out ␦F508/dF508 A,D 13 15 5.8 41 In ␦F508/dF508 A,D,E 14 26 12.7 88 Out ␦F508/dF508 A,D 15 11 16.3 72 Out ␦F508/W1282X A,D 16 18 10.0 58 In ␦F508/dF508 A,D 17 22 10.5 50 Out ␦F508/dF508 A,D 18 35 8.6 87 Out ␦F508/C276X A,E 19 17 16.2 62 In ␦F508/dF508 B,E 20 14 4.1 85 In ␦F508/dF508 B 21 22 2.3 62 In ␦F508/G542X B 22 21 7.7 54 In ␦F508/N1303K B 23 19 2.4 69 In ␦F508/Y1092X B 24 19 4.6 87 In ␦F508/dF508 B, C, E 25 21 8.2 58 In R334W/unk C 26 22 5.8 85 In ␦F508/dF508 C,E 27 22 2.9 67 In unk/unk C 28 20 6.7 77 In ␦F508/dF508 E 29 18 13.3 92 In ␦F508/dF508 E 30 22 8.8 71 In ␦F508/394delTT E 31 15 13.0 68 In ␦F508/dF508 E 32 14 unk 97 Out ␦F508/dF508 E unk indicates unknown.
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ABCC7 p.Asn1303Lys 15705796:44:545
status: NEW
X
ABCC7 p.Asn1303Lys 15705796:44:1024
status: NEW
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PMID: 15709055 [PubMed] Sermet-Gaudelus I et al: "Chloride transport in nasal ciliated cells of cystic fibrosis heterozygotes."
No. Sentence Comment
56 Most of the mutations observed in heterozygous subjects were class II: ⌬F508 (n ϭ 40) and N1303K (n ϭ 2) mutations.
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ABCC7 p.Asn1303Lys 15709055:56:103
status: NEW
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PMID: 15738290 [PubMed]