ABCMdb

PMID: 19897426

Picci L, Cameran M, Marangon O, Marzenta D, Ferrari S, Frigo AC, Scarpa M
A 10-year large-scale cystic fibrosis carrier screening in the Italian population.
J Cyst Fibros. 2010 Jan;9(1):29-35. Epub 2009 Nov 7., [PubMed]

Sentences

No. Mutations Sentence Comment

48 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly1244Glu ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Arg352Gln ABCC7 p.Glu585* ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Thr338Ile ABCC7 p.Leu1065Pro ABCC7 p.Arg1158* ABCC7 p.Met1101Lys ABCC7 p.Gln552* ABCC7 p.Asp1152His ABCC7 p.Leu1077Pro ABCC7 p.Arg1066His ABCC7 p.Asp110His ABCC7 p.Arg334Gln ABCC7 p.Arg709* ABCC7 p.Asp579Gly ABCC7 p.Ser466* ABCC7 p.Glu527Gly Forty-seven different CFTR mutations/gene alterations were chosen and analysed: ΔF508, G85E, 541delC, D110H, R117H, 621+1G→T, 711+5G→A, R334W, R334Q, T338I, R347H, R347P, R352Q, S466X, ΔI507, E527G, 1717-1G→A, 1717-8G→A, G542X, S549N, S549R A→C, G551D, Q552X, R553X, D579G, 1874insT, E585X, 1898+3A→G, 2183AA→G, 2184delA, R709X, 2789+5G→A, 3132delTG, 3199del6, 3272-26A→G, L1077P, L1065P, R1066H, M1101K, D1152H, R1158X, R1162X, 3849+10KbC→T, G1244E, W1282X, N1303K and 4016insT. Login to comment 74 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Leu206Trp ABCC7 p.Val201Met ABCC7 p.Ser42Phe ABCC7 p.Arg352Trp ABCC7 p.Leu1414Ser ABCC7 p.Ala238Val For many of these subjects mutations were identified following DGGE and/or dHPLC analysis, and not through the RDB-based test, as gene alterations are "rare"/uncommon [A238V, R352W, S42F, (V201M, D1270N & R74W) and L206W] or because they have never been identified before [D372E (1251T→G) and L1414S (4373T→C)]. Login to comment 76 ABCC7 p.Arg117His For example, the compound heterozygote ΔF508/R117H, previously reported to occur commonly in CBAVD and infertile patients [20,21], was also a frequent genotype in our study (Table 2b). Login to comment 89 ABCC7 p.Arg117His ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1445Asn ABCC7 p.Ser42Phe ABCC7 p.Glu527Gly ABCC7 p.Glu527Gly Mutations found in the homozygous (n=2) and heterozygous (n=20) diagnosed foetuses are the following: ΔF508/ΔF508 (n=1), 711+5G→A/711+5G→A (n=1), ΔF508/P5L (n=1), 2183AA→G/S42F (n=1), ΔF508/ D1445N (n=1), 711+5G→A/ΔF508 (n=1), G542X/E527G (n=1), N1303K/1717-1 G→A (n=1), R117H/E527G (n=1), ΔF508/2183AA→G (n=1), ΔF508/D1152H (n=1), R347H/ ΔF508 (n=1), ΔF508/G542X (n=2), ΔF508/N1303K (n=2), R1162X/ΔF508 (n=3), N1303K/D1152H (n=3). Login to comment 97 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347His ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Gly85Glu ABCC7 p.Thr338Ile ABCC7 p.Arg1158* ABCC7 p.Arg1070Gln ABCC7 p.Gln552* ABCC7 p.Asp1152His ABCC7 p.Val201Met ABCC7 p.Arg1066His ABCC7 p.Asp110His ABCC7 p.Arg334Gln ABCC7 p.Arg334Gln ABCC7 p.Ser42Phe ABCC7 p.Glu527Gly ABCC7 p.Arg352Trp ABCC7 p.Leu1414Ser ABCC7 p.Ala238Val CF mutation General adult population MAR population n=1879 n=236 ΔF508 42.6 45.7 2183AA→G 5.9 5.9 R1162X 5.7 8.2 N1303K 5.4 5.9 G542X 4.2 3.7 D1152H 3.9 5.0 R553X 3.7 3.1 R117H 3.3 1.8 711+5G→A 2.8 4.1 Q552X 2.8 0.4 2789+5G→A 2.2 3.1 1717-1G→A 2.6 2.8 E527G 2.4 - G85E 2.4 0.9 R334Q 0.9 0.4 W1282X 0.7 0.9 R334W 0.6 - 1898+3A→G 0.5 0.4 R1158X 0.4 - R1066H 0.4 0.4 T338I 0.4 1.8 3849+10Kb C→T 0.4 1.3 3272-26 A→G - 0.9 3132delTG - 0.9 3659 del C - 0.4 4016 ins T - 0.4 1717-8G→A - 0.4 R347H - 0.4 ΔI507 - 0.4 R1070Q - 0.4 Other (16) 5.4 - Table 2a List of CFTR compound heterozygotes in the adult general population. Mutation Health status Disorder Gender Age (years) Notes and refs ΔF508/A238V Infertile CBAVD M 36 (A) ΔF508/R352W Infertile CBAVD M 45 (A) R553X/R334Q M 38 ΔF508/R347H M 53 [17] S42F/D372E (1251T→G) M 39 (A) (B) ΔF508/D110H Infertile M 38 ΔF508/L1414S (4373T→C) Infertile CBAVD M 44 (A) (B) ΔF508/V201M, D1270N & R74W Infertile CBAVD M 44 (A) [18,19] 2183AA→G/L206W Infertile CBAVD M 40 (A) 711+5G→A/ L206W Infertile CBAVD M 40 (A) Table 2b List of CFTR compound heterozygotes in the population enrolled for medically assisted reproduction. Login to comment 98 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Arg1066His ABCC7 p.Asp110His Mutation Disorder Gender Age (years) Notes and refs ΔF508/R117H M 47 (C) [20,21] ΔF508/R117H F 36 (C) [20,21] ΔF508/R117H M 43 (C) [20,21] G542X/D1152H M 40 (C) R1162X/2789+5G→A CBAVD M 44 (C) R117H/2789+5G→A CBAVD M 42 (C) N1303K/D110H CBAVD M 32 (C) N1303K/D1152H M 40 (C) 2789+5G→A/R1066H M 40 (C) Abbreviations: CBAVD: Congenital Bilateral Absence of the Vas Deference; M: Male; F: Female. Login to comment 99 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Leu206Trp ABCC7 p.Val201Met ABCC7 p.Ser42Phe ABCC7 p.Arg352Trp ABCC7 p.Leu1414Ser ABCC7 p.Ala238Val Notes to Tables: (A) CFTR mutations A238V, R352W, 4006-19del3, S42F, D372E (1251T→G), L1414S (4373T→C), (V201M, D1270N & R74W) and L206W are not included in the RDB-based screening. Login to comment 101 ABCC7 p.Leu1414Ser (B) D372E (1251T→G) and L1414S (4373T→C) are CFTR mutation that have never been described before (see Table 4). Login to comment 105 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Arg1066His ABCC7 p.Asp110His Among the subjects tested, 9 resulted to be compound heterozygotes: ΔF508/R117H (n=3), G542X/D1152H (n=1), R1162X/2789+5G→A (n=1), R117H/2789 + 5G→A (n = 1), N1303K/D110H (n = 1), N1303K/D1152H (n = 1), 2789 + 5G→A/R1066H (n = 1) (Table 2b). Login to comment 106 ABCC7 p.Arg117His ABCC7 p.Arg117His The identification of 3 subjects with ΔF508/ R117H confirmed findings from other studies reporting high frequencies of ΔF508/R117H compound heterozygotes in males with infertility problems [20,21]. Login to comment 111 ABCC7 p.Ile148Thr Differently from previous reports, point mutation I148T was never found in close association with 3199del6 and similarly 3601-111 G→C with 1811+1,2KB A→G. Login to comment 130 ABCC7 p.Ile148Thr ABCC7 p.Ser1235Arg ABCC7 p.Phe1052Val ABCC7 p.Leu997Phe Recently, a study of 335,204 patients screened for their CF carrier status revealed 4 individuals with Table 3 Frequency of less common CFTR mutations in the general population. Mutation Frequency Reference S1235R 1/77 [22,23] L997F 1/77 [24] I148T 1/129 [19] F1052V 1/200 [25] 621+3A→G 1/335 [26] 3601-111 G→C 1/690 [27] Table 4 New CFTR mutations found in the general population following 2nd level analysis. Login to comment 131 ABCC7 p.Ala349Val ABCC7 p.Asp806Gly ABCC7 p.Val920Leu ABCC7 p.Ser911Arg ABCC7 p.Pro1290Thr ABCC7 p.Ser660Thr ABCC7 p.Ser431Gly ABCC7 p.Tyr1381His ABCC7 p.Leu1414Ser ABCC7 p.Leu1335Phe ABCC7 p.Ile840Thr ABCC7 p.Gln1352Glu ABCC7 p.Asn416Ser ABCC7 p.Met348Thr ABCC7 p.Ile807Val ABCC7 p.Asp674Val ABCC7 p.Ile586Val ABCC7 p.Gln1268Arg ABCC7 p.Thr788Ile ABCC7 p.Tyr84His ABCC7 p.Leu1480Pro ABCC7 p.Pro355Ser ABCC7 p.Thr1263Ala Aminoacid change Nucleotide change A349V 1178C→T D372E 1251T→G D674V 2153A→T D806G 2549A→G I586V 1888A→G I807V 2551A→G I840T 2651T→C L1335F 4135C→T L1414S 4373T→C L1480P 4571T→C M348T 1175T→C N416S 1379A→G P1290T 4000C→T P355S 1195C→T Q1268R 3935A→G Q1352E 4186C→G S431G 2423A→G S660T 2110T→A S911R 2865T→G T1263A 3919A→G T788I 2495C→T V920L 2890G→T Y1381H 4273T→C Y84H 382T→C two CFTR mutations and who had not been previously diagnosed with CF [29]. Login to comment 135 ABCC7 p.Arg117His The most striking example is the length of the intron 8 polythydimine tract on exon 9 splicing as genetic modifier of the severity of the R117H mutation. Login to comment 137 ABCC7 p.Asp1270Asn ABCC7 p.Ile148Thr In North America, for example, missense mutations I148T and D1270N were found N100 and N200 times, respectively, more frequently in CF carriers than in patients. Login to comment 139 ABCC7 p.Gly542* ABCC7 p.Ser1235Arg In our study a rare mutation such as S1235R was found to be moderately frequent (1/77) and despite being normally classified as "mild", association with a second CFTR gene mutation (G542X) can lead to idiopathic chronic pancreatitis [23]. Login to comment 140 ABCC7 p.Ile148Thr Similarly, I148T was shown to be associated with a CF phenotype only when associated with mutation 3199del6 on the same gene [19]. Login to comment