ABCMdb

ABCC7 p.Ala1067Thr

[switch to full view]
Comments [show]

II-III (maturation defect, gating defect) <a href="https://www.ncbi.nlm.nih.gov/pubmed/26823392">Veit et al.</a>
admin on 2016-08-19 15:16:22

Publications

PMID: 11242048 [PubMed] Choi JY et al: "Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis."

No. Sentence Comment

36 Similar rates were measured for the I148T, G178R, A1067T, G1244E, S1255P and G1349D mutants (see Fig. 3 for location of these mutations in CFTR), all of which are associated with CF with pancreatic insuf®- ciency. Login to comment
186 letters to nature 96 NATURE |VOL 410 |1 MARCH 2001 |www.nature.com HCO3 -/Cl- transportratio 0 0.25 0.50 0.75 1.00 WT I148T G178R R297Q G551D H620Q G970R A1067T G1244E S1255P G1349D E193K G551S A800G H949Y R1070Q Pancreatic insufficient Pancreatic sufficientD648V N CI148T G178R E193K R297Q R117H A1067T R1070Q G1244E S1255P G1349D NBD2 RD H949Y G970R CL4CL3CL2CL1 NBD1 G551D G551S H620Q D648V A800G Figure 3 The HCO3:Cl-transport ratio of CFTR mutants associated with CF. Login to comment

PMID: 18193900 [PubMed] Cheung JC et al: "Misfolding of the cystic fibrosis transmembrane conductance regulator and disease."

No. Sentence Comment

90 In some additional examples, a number of mutations found in the fourth intracellular loop (H1054D, G1061R, L1065P, R1066C/H/L, Q1071P, L1077P, H1085R, W1098R, M1101K/ R) also affect the biosynthetic processing of CFTR (although function was not tested) (73); some intracellular loop 4 mutants (F1052V, K1060T, A1067T, G1069R, R1070Q/W) can process CFTR to the complex-glycosylated ("Band C") form but have altered channel activity compared to wild type. Login to comment

PMID: 9895335 [PubMed] Cremonesi L et al: "Validation of double gradient denaturing gradient gel electrophoresis through multigenic retrospective analysis."

No. Sentence Comment

31 Mutations and polymorphisms analyzed in the CFTR gene. Position Denaturant gradient Mutation Exon 1 40-90% 125G/Ca,b M1V (A3G at 133) 175insT 182delT Exon 3 10-60% W57G (T3G at 301) 356G/Aa G85E (G3A at 386) Exon 4 20-70% R117H (G3A at 482) 541delC 621ϩ1G3T I148T (T3C at 575) Exon 5 20-70% E193K (G3A at 709) Intron 5 20-70% 711ϩ3A3G Exon 7 20-70% 1078delT R334W (C3T at 1132) T338I (C3T at 1145) R347P (G3C at 1172)b R347H (G3A at 1172) R352Q (G3A at 1187) Exon 10 20-70% M470V (1540A/G)a ⌬F508 (del 3 bp at 1652) Intron 10 10-60% 1717-1G3A Exon 11 10-60% G542X (G3T at 1756) 1784delG R553X (C3T at 1789) Exon 12 10-60% D579G (A3G at 1868) E585X (G3T at 1885) Intron 12 10-60% 1898ϩ3A3G Exon 13 30-80% 2183AA3G E730X (G3T at 2320) L732X (T3G at 2327) 2347delG Exon 14a 10-60% T854T (2694T/G)a V868V (2736G/A)a Intron 14b 30-80% 2789ϩ5G3A Exon 15 20-70% M952I (G3C at 2988)b Exon 17a 20-70% L997F (G3C at 3123)b Exon 17b 20-70% F1052V (T3G at 3286) R1066C (C3T at 3328) R1066H (G3A at 3329) A1067T (G3A at 3331) Exon 18 20-70% D1152H (G3C at 3586)b Exon 19 30-80% R1158X (C3T at 3604) Exon 20 20-70% S1251N (G3A at 3384) W1282X (G3A at 3978) Exon 21 20-70% N1303K (C3G at 4041)b Exon 22 30-80% G1349D (G3A at 4178) 4382delA Exon 24 30-80% Y1424Y (4404C/T)a a Polymorphism. Login to comment

PMID: 18687795 [PubMed] Audrezet MP et al: "Validation of high-resolution DNA melting analysis for mutation scanning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene."

No. Sentence Comment

63 Continued Exon Primer Sequences GC length Amplicon length (bp) Introns Number of heterozygous- positive controls Number of homozygous- positive controls Recommended control 16 LSCFE16Fmod 5Ј-CCGCTGAATGCGTCTACTGTGATCCA-3Ј 3 299 bp 77 6 G970R LSCFE16Rmod 5Ј-CCGTAGACAGGACTTCAA CCCTCAATCAA-3Ј 3 87 3120ϩ1GϾA 17a LSCFE17AFmod 5Ј-CCGCCGGACACACTTTG TCCACTT-3Ј 6 286 bp 49 13 3121-1GϾA LSCFE17ARmod 5Ј-CCGCCGTCAAATAGCTCTTATAGCTTTTTT ACAAGATG-3Ј 6 25 I1027T 17b LSCF17BAFmod 5Ј-CCGCCGCCCCGCCGTCAGGTACA AGATATTATG-3Ј 14 56 11 3272-26AϾG LSCF17BARmod 5Ј-CCGCCGCCGCAGTGTTGACAGGT ACAAGAAC-3Ј 7 247 bp A1067T LSCF17BBFmod 5Ј-CCGCCCTTACTTTGAAACTCTGTT CCACAAAGC-3Ј 4 247 bp T1095T LSCF17BBRmod 5Ј-CCGCCGTTGATAACCTATAGAATG CAG-3Ј 6 62 E1104X 18 LSCFE18Fmod 5Ј-CCGCCGAGTCGTTCACAGAAGA GAGAAATAAC-3Ј 6 236 bp 34 2 D1152H LSCFE18Rmod 5Ј-CCGCCGCCGCGGTACTTTGTT ACTTGTCTGAATTTTTTT-3ЈCATAA 12 25 3547delA 19 LSCF19i5mod 5Ј-CCGCCGCCGCGCATCAAACTA ATTGTGAAATTGTCTGCC-3Ј 10 408 bp 73 10 S1235R LSCF19i3mod 5Ј-CCGCCGCCGCACACATTGCT TCAGGCTACTGGGA-3Ј 11 49 R1162L 20 LSCF20i5mod 5Ј-CCGCCGCCGCCGCTACTGAATTATGT TTATGGCATGG-3Ј 13 323 bp 44 13 W1282X LSCF20i3mod 5Ј-CCGCCGCCGCTCTTGAGTACAAGTA TCAAATAGCAG-3Ј 10 50 4005ϩ33GϾA 21 LSCFe21F 5Ј-CCGCCGCCGCGCAAGTTATTCATA CTTTCTTCTTCTTT-3Ј 12 217 bp 15 5 1 N1303K LSCFe21R 5Ј-CCGCCGCCGCTATATCAGCCA TTTGTG-3Ј 8 47 Q1313X 22 LSCFe22FmodC LSCFe22 RmodD 5Ј-CCGCCGAGAATGTCAAC TGCTTGAGTGT-3Ј 6 311 bp 41 2 R1358S 5Ј-CCGCCGGCAGGCATAATGA TTCTGTTCCCAC-3Ј 10 51 I1366T 23 LSCFE23Fmod 5Ј-CCGCCGCCGCAAGGTAAAT ACAGATCAT-3Ј 9 259 bp 44 3 4374ϩ1GϾT 4374ϩ13AϾG LSCFE23Rmod: 5Ј-CCGGCAGGAACTATCACAT GTGAGATTG-3Ј 3 53 24 LSCFE24FmodB 5Ј-CCGCCGCTTTGAGCCTGT GCCAGTTTCTGT-3Ј 6 378 bp 58 5 1 Q1463Q LSE24RmodB 5Ј-CCGCCGACGAGCTCCAATTC CATGAGGTGA-3Ј 6 62 Y1424Y the same technique: the majority of our samples were extracted by a classical saline technique or an automated extraction and their quality was adequate. Login to comment

PMID: 10649505 [PubMed] Yee K et al: "Novel Cystic Fibrosis mutation L1093P: functional analysis and possible Native American origin."

No. Sentence Comment

78 Other mutations in this region e.g. A1067T (Cotton et al. 1996; Seibert et al. 1996) and Q1071P (Seibert et al. 1996) are associated with pancreatic insufficiency, yet retain partial function when tested with efflux assays. Login to comment

PMID: 10923036 [PubMed] Claustres M et al: "Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France."

No. Sentence Comment

109 h M1K, K14X, W19X, 211delG, G27E, R31C, 237insA, 241delAT, Q39X, 244delTA, 296+2T>C, 297-3C>T, W57X+F87L, 306delTAGA, P67L, A72D, 347delC, R75Q, 359insT, 394delT, 405+4A>G, Q98R, 457TAT>G, R117H+5T, R117H+I1027T, R117L, R117P, H139R, A141D, M152V, N186K, D192N, D192del, E193X, 711+1G>A, 711+3A>G, 712-1G>T, L206F, W216X, C225R, Q237E, G241R, 852del22, 876-14del12, 905delG, 993del5, E292K, Y304X, F311del, 1161delC, R347L, R352Q, W361R, 1215delG, S364P, S434X, D443Y, S466X, C491R, T501A, I506T, F508C, I507del+F508C, F508del+L467F, 1774delCT, R553G, 1802delC, 1806delA, A559E, Y563N, 1833delT, Y569C, Y569H, Y569X, G576X, G576A, T582I, 1898+3A>G+186-13C>G, 1918delGC, R600G, L610S, G628R, 2043delG, 2118del4, E664X, 2174insA, Q689X, K698R, K716X, L732X, 2347delG, 2372del8, R764X, 2423delG, S776X, 2634insT, 2640delT, C866Y, 2752-1G>T, W882X, Y913C, V920M, 2896insAG, H939D, H939R, D979V, D985H, D993Y, 3120G>A, I1005R, 3195del6, 3293delA, 3320ins5, W1063X, A1067T, 3359delCT, T1086I, W1089X, Y1092X+S1235R, W1098X, E1104X, R1128X, 3532AC>GTA, 3548TCAT>G, M1140del, 3600G>A, R1162L, 3667ins4, 3732delA+K1200E, S1206X, 3791delC, S1235R+5T, Q1238R, Q1238X, 3849+4A>G, T1246I, 3869insG, S1255P, R1283K, F1286S, 4005+1G>T, 4006-8T>A, 4015delA, N1303H, N1303I, 4172delGC, 4218insT, 4326delTC, Q1382X, 4375-1C>T, 4382delA, D1445N, CF40kbdel4-10, Cfdel17b. Login to comment
113 Eleven mutations were reported as ''complex alleles,`` particularly in chromosomes carrying the 5T allele, although several changes (G576A, R668C, A1067T) are considered as neutral polymorphisms (CFGAC). Login to comment
129 Six sequence changes listed as mutations (CFGAC or personal communication) were detected on a chromosome carrying the 5T allele (G550R, A800G, T1053I, A1067T, S1235R, and 1717- 3T>G). Login to comment
152 Twenty-four non F508del mutations were found associated with the 9T allele: 394delTT, L90S, D110H, R117G, 621+1G>T, V232D, A455E, G542X, R851L, T908N, 2789+5G>A, 2896insAG, H939R, 3007delG, I980K, I1027T, R1066H, A1067T, D1154G, 3737delA, R74W+D1270N, N1303I, N1303K, D1377H. Login to comment

PMID: 10200050 [PubMed] de Meeus A et al: "Genetic findings in congenital bilateral aplasia of vas deferens patients and identification of six novel mutatations. Mutations in brief no. 138. Online."

No. Sentence Comment

6 Fourty-two of the 64 patients (65.6%) had mutations on both copies of the CFTR gene, including one patient with two mutations in the same copy (DF508 + A1067T). Login to comment
31 A double mutant allele was identified in one CBAVD patient (N°38 in table 1) with the DF508 associated to the mutation A1067T on the same chromosome inherited from his father, in trans with the 5T allele inherited from his mother. Login to comment

PMID: 9511929 [PubMed] Devidas S et al: "CFTR: domains, structure, and function."

No. Sentence Comment

98 A mutation in the adjacent residue A1067T caused a decrease in the P0 with a corresponding decrease in the burst duration. Login to comment

PMID: 8702904 [PubMed] Cotten JF et al: "Effect of cystic fibrosis-associated mutations in the fourth intracellular loop of cystic fibrosis transmembrane conductance regulator."

No. Sentence Comment

84 In Fig. 2 the processing of ⌬F508 and the milder CF-associated mutant, P574H (10), are provided for reference. Login to comment
85 Whole Cell Function of ICL4 Mutants-To evaluate the effect of ICL4 mutations on Cl- channel activity, we selected the mutants R1066C, R1066H, R1066L, A1067T, and F1052V for study. Login to comment
95 We found that cells expressing all of the ICL4 mutants (F1052V, R1066C, R1066H, R1066L, and A1067T) generated cAMP-stimulated Cl- selective currents that showed time-and voltage-independent behavior identical to that of wild-type CFTR (data not shown). Login to comment
103 Mutations did not alter single-channel conductance: wild-type, 8.9 Ϯ 0.3 pS; F1052V, 9.6 Ϯ 0.2 pS; R1066C, 8.9 Ϯ 0.4 pS; R1066H, 8.5 Ϯ 0.7; R1066C, 8.6 Ϯ 0.3; and A1067T, 9.2 Ϯ 0.2 pS. Login to comment
105 Table I shows that F1052V, R1066L, and A1067T did not alter the relative permeability or conductivity sequence for Cl- , Br- , or I- . Login to comment
115 In contrast to the cysteine mutation, mutation of Arg-1066 to histidine did not significantly alter any of the kinetics and mutation to leucine produced a small decrease in burst duration and increase in fast closed time. Login to comment
116 Mutation of the adjacent residue Ala-1067 to threonine produced a different pattern; Po was decreased primarily because of a decrease in burst duration. Login to comment
134 R1066L and A1067T because they showed altered gating (Figs. 4 and 5); we did not study R1066C because it was difficult to study in excised, inside-out membrane patches, possibly because of its very low Po and poor processing. Login to comment
136 R1066L had a response identical to that of wild-type CFTR. Login to comment
137 The maximum Po of A1067T was decreased, but the shape of the concentration Po curve mirrored that of wild-type. Login to comment
139 This pattern of response for A1067T is similar to what we have found with the NBD mutants G551D, G1244E, and G1349D (8). Login to comment
140 The decrease in maximum Po without a change in the shape of the dose-response curve suggests that in A1067T ATP binding may be unaltered but that a step distal to binding may be affected. Login to comment
152 n Px/PCL Gx/GCL Br- Cl- IBr- ClI- Wild-type 3 1.29 Ϯ 0.07 1.00 0.56 Ϯ 0.13 1.18 Ϯ 0.56 1.00 0.35 Ϯ 0.06 F1052V 2 1.41 1.00 0.50 0.98 1.00 0.53 R1066L 4 1.36 Ϯ 0.07 1.00 0.88 Ϯ 0.11 1.15 Ϯ 0.22 1.00 0.40 Ϯ 0.11 A1067T 4 1.29 Ϯ 0.15 1.00 0.66 Ϯ 0.04 1.00 Ϯ 0.10 1.00 0.43 Ϯ 0.06 FIG. 4. Login to comment
156 Data are mean Ϯ S.E. of (6/5) measurements for Po and burst duration, respectively: wild-type (19/18), F1052V (6/5) R1066C (3/3), R1066H (6/7), R1066L (12/5), and A1067T (9/3). Login to comment
189 The fact that ICL4 and NBD2 mutants reduced the response to PPi and the finding that G1349D and A1067T altered the effect of increasing concentrations of ATP in a similar way further suggest some interaction between ICL4 and the NBDs, particularly NBD2. Login to comment
200 Data are mean Ϯ S.E. of (n) measurements for: wild-type (9), F1052V (3), R1066L (4), A1067T (4), G551S (6), K464A (4), G1349D (5), K1250 M at 5 mM PPi (5), wild-type at 5 mM PPi (16). Login to comment
202 Effect of increasing concentrations of ATP on Po for wild-type CFTR (squares), R1066L (circles), and A1067T (triangles). Login to comment
222 For example, H1085R is misprocessed like ⌬F508, yet it is reported to occur in a patient with a pancreatic sufficient phenotype. Login to comment
223 Conversely, our data with the mutants R1066L, R1066H, and A1067T are similar to that obtained with the "mild" mutants A455E and P574H (10) in that they retained partial processing and function. Login to comment
94 We found that cells expressing all of the ICL4 mutants (F1052V, R1066C, R1066H, R1066L, and A1067T) generated cAMP-stimulated Cl2 selective currents that showed time-and voltage-independent behavior identical to that of wild-type CFTR (data not shown). Login to comment
102 Mutations did not alter single-channel conductance: wild-type, 8.9 6 0.3 pS; F1052V, 9.6 6 0.2 pS; R1066C, 8.9 6 0.4 pS; R1066H, 8.5 6 0.7; R1066C, 8.6 6 0.3; and A1067T, 9.2 6 0.2 pS. Login to comment
104 Table I shows that F1052V, R1066L, and A1067T did not alter the relative permeability or conductivity sequence for Cl2 , Br2 , or I2 . Login to comment
133 CF-associated Mutations in ICL4 of CFTR R1066L and A1067T because they showed altered gating (Figs. 4 and 5); we did not study R1066C because it was difficult to study in excised, inside-out membrane patches, possibly because of its very low Po and poor processing. Login to comment
138 This pattern of response for A1067T is similar to what we have found with the NBD mutants G551D, G1244E, and G1349D (8). Login to comment
151 n Px/PCL Gx/GCL Br2 Cl2 I2 Br2 Cl2 I2 Wild-type 3 1.29 6 0.07 1.00 0.56 6 0.13 1.18 6 0.56 1.00 0.35 6 0.06 F1052V 2 1.41 1.00 0.50 0.98 1.00 0.53 R1066L 4 1.36 6 0.07 1.00 0.88 6 0.11 1.15 6 0.22 1.00 0.40 6 0.11 A1067T 4 1.29 6 0.15 1.00 0.66 6 0.04 1.00 6 0.10 1.00 0.43 6 0.06 FIG. 4. Login to comment
155 Data are mean 6 S.E. of (6/5) measurements for Po and burst duration, respectively: wild-type (19/18), F1052V (6/5) R1066C (3/3), R1066H (6/7), R1066L (12/5), and A1067T (9/3). Login to comment
188 The fact that ICL4 and NBD2 mutants reduced the response to PPi and the finding that G1349D and A1067T altered the effect of increasing concentrations of ATP in a similar way further suggest some interaction between ICL4 and the NBDs, particularly NBD2. Login to comment
199 Data are mean 6 S.E. of (n) measurements for: wild-type (9), F1052V (3), R1066L (4), A1067T (4), G551S (6), K464A (4), G1349D (5), K1250 M at 5 mM PPi (5), wild-type at 5 mM PPi (16). Login to comment
201 Effect of increasing concentrations of ATP on Po for wild-type CFTR (squares), R1066L (circles), and A1067T (triangles). Login to comment

PMID: 8662892 [PubMed] Seibert FS et al: "Disease-associated mutations in the fourth cytoplasmic loop of cystic fibrosis transmembrane conductance regulator compromise biosynthetic processing and chloride channel activity."

No. Sentence Comment

64 The mature forms of the other six mutants (F1052V, K1060T, A1067T, G1069R, R1070W, R1070Q) were produced in relatively normal amounts (band C), although for A1067T and R1070W CFTR the ratio of the complex-glycosylated to core-glycosylated bands was significantly lower than for wild-type CFTR. Login to comment
82 A1067T, R1070W, and R1070Q CFTR had significantly lower efflux levels and significantly lower protein expression than wild-type CFTR in COS-1 cells. Login to comment
127 Symbols are as follows: A: छ, WT; E, F1052V; Ç, K1060T; µ, A1067T; Ⅺ, vector only control. Login to comment
142 A, examples of wild-type, F1052V, K1060T, A1067T, G1069R, R1070Q, and R1070W CFTR single channel currents recorded from inside-out membrane patches at a membrane potential of -30 mV. Login to comment
71 The mature forms of the other six mutants (F1052V, K1060T, A1067T, G1069R, R1070W, R1070Q) were produced in relatively normal amounts (band C), although for A1067T and R1070W CFTR the ratio of the complex-glycosylated to core-glycosylated bands was significantly lower than for wild-type CFTR. Login to comment
89 A1067T, R1070W, and R1070Q CFTR had significantly lower efflux levels and significantly lower protein expression than wild-type CFTR in COS-1 cells. Login to comment
133 Symbols are as follows: A: L, WT; E, F1052V; &#c7;, K1060T; &#b5;, A1067T; M, vector only control. Login to comment
148 A, examples of wild-type, F1052V, K1060T, A1067T, G1069R, R1070Q, and R1070W CFTR single channel currents recorded from inside-out membrane patches at a membrane potential of 230 mV. Login to comment

PMID: 8530001 [PubMed] Ferec C et al: "Neonatal screening for cystic fibrosis: result of a pilot study using both immunoreactive trypsinogen and cystic fibrosis gene mutation analyses."

No. Sentence Comment

82 {17bi DI507 [ Y569X W846X 2789+5G->A ,' $492F i ] i I G551D 2622+1 G->A Y1092X 1717-1 G->A E827X A1067T G542X 2183 AA->G R1066H R560K 2184 ins A 3320,ins 5 R553G R1070W 1806 del A & 4005+1G->A W1282X ] i "- Exons Fig.2 Distribution of the different mutations (except AF508) of the CFTR gene in Brittany Table 1 Mutations and genotypes in newborns Genotypes of newborns Number Sweat test AF508/AF508 7 + > 90 AF508/1806 del A 1 + > 90 R553G/G551D 1 Borderline (60) AF508/G551D 1 + > 90 AF508/R1070W 1 40 AF508/G542X 1 + > 90 AF508/G149R 1 45 Total 13 Mutations found in heterozygote newborns AF508 31 R560K 1 1078 del T 1 G544S l G542X 1 V317A 1 R347H 1 V322A 1 Total 38 gene. Login to comment

PMID: 7543317 [PubMed] Pignatti PF et al: "Increased incidence of cystic fibrosis gene mutations in adults with disseminated bronchiectasis."

No. Sentence Comment

31 List of CFTR gene mutations and DNA polymorphisms screened Mutations R75Q/X/L, G85E, 394deITT 457TAT->G, R117H 621 + 1G->T 711 + 5G->A L206W 875 + 40 A->G 936 del TA 1001 + 11C->T R334W, R347 P/H/L, 1154insTC A455E, V456F DF5O8 1717-IG->A, 1717-8G->A G542X, G551D, Q552X, R553X P574H 1898 + 3A->G 2183 AA->G, 2184delA, R709X D836Y, 2694 T/G 2752-22 A/G 2789 + 5 G->A, 2790-2 A-»G Q890X 3041-71 G/C 3132delTG 3271 + 18 C-»T, 3272-26 A->G H1054D, G1061R, R1066C/H, A1067T, H1085R, Y1092X, 3320 ins5 D1152H R1162X, 3667ins4, 3737delA, 11234V 3849 + 10 kb C-»T, 3850-1 G-»A SI25IN, S1255P, 3905insT, 3898insC, D127ON, W1282X, R1283M, 4002 A/G 4005 + 1 G-»A N1303 K/H, 4029 A/G D1377H Q1411 X 4404 C/T, 4521 G/A Location e 3 e 4 i 4 i 5 e 6a i 6a e 6b i 6b e 7 e 9 e 10 i 10 e 11 e 12 i 12 e 13 e 14a i 14a i 14b e 15 i 15 e 17a i 17a e 17b e 18 e 19 i 19 e 20 i 20 e2l e 22 e 23 e24 Listing is in order of location along the CFTR gene, e = exon; i = intron. Login to comment

PMID: 7529319 [PubMed] Mercier B et al: "A cluster of cystic fibrosis mutations in exon 17b of the CFTR gene: a site for rare mutations."

No. Sentence Comment

19 Most of these are missense mutations and as no functional test has been 732 Table 1 Mutations identified in exon 17b of the CFTR gene Mutation Nucleotide Modificationl Ethnic Rcferencesposition ongini (No) 3271-1 G--A 3272-1 G-A Belgian (1) 11F1052V 3286 T-G Belgian (1) 11HI054D 3292 CG French (1) 13G1061R 3313 G-C French (1) 113320 Dup 3320 Duplication of Breton (1) 6 CTATG R1066C 3328 CT French (1) 14 R1066L R1066H A1067T G1069R R1070Q 3359 del CT L1077P H1085R W1089X Y1092X M1IOIR 3329 3329 3331 3337 3341 G-T G-+A G-A G,A G--A 3359 3362 3386 3398 3408 3434 del CT T--C A-.G G-+A C +A T--G Spanish (5) French (1) Breton (1) Breton (1) Bulgarian (1) Bulgarian (3) Rumanian (1) Albanian (1) French (1) Italian (1) French (1) Spanish (1) French (4) Turkish (1I) * Bozon et al, personal communication. Login to comment

PMID: 7521710 [PubMed] Ravnik-Glavac M et al: "Sensitivity of single-strand conformation polymorphism and heteroduplex method for mutation detection in the cystic fibrosis gene."

No. Sentence Comment

121 1078delT (35), L327R (Ravnik-Glavac a al., unpublished), R334W (36), D36K (31), R347L (26), R347P (14), A349V (26), R352Q (30), 1221delCT (34); Exon 8: W401X (31), 1342-1G-C (25); Exon 9: G458V (37), 1525 -1G-A (38); Exon 10: S492F (34), Q493X (39), 1609delCA (40,17), deltaI507 (39,41), deltaF5O8 (3), 1717-1G-A (39,42); Exon 11: G542X (39), S549N, G551D, R553X (43), R553Q (44), A559T (43), R560K (Fine et al., pers. comm.), R560T (39); Exon 12: Y563N (39), 1833delT (Schwartz et al., pers. comm.), P574H (39), 1898 + 1G-C (31), 1898+3A-G (Ferrari et al., pers. comm.); Exon 13: G628R(G-C) (31), Q685X (Firec et al., pers. comm.), K716X (26), L719X (Dork etal., pers. comm.), 2522insC (15), 2556insAT (45), E827X (34); Exon 14a: E831X (Ffrec et al., pers. comm.), R851X (29), 2721delll (31), C866Y (Audrezet et al., pers. comm.); Exon 14b: 2789+5G-A (Highsmith et al., pers. comm.); Exon 15: 2907denT (21), 2991del32 (Dark and TQmmler, pers. comm.), G970R (31); Exon 16: S977P, 3100insA (D6rk et al., pers. comm.); Exon 17a: I1005R (Dork and TQmmler, pers. comm.), 3272-1G-A (46); Exon 17b: H1054D (F6rec et al., pers. comm.), G1061R (Fdrec et al., pers. comm.), 332Oins5, R1066H, A1067T (34), R1066L (Fe"rec etal., pers. comm.), R1070Q (46), E1104X (Zielenski el al., pers. comm.), 3359delCT (46), L1077P (Bozon « a/., pers. comm.), H1085R (46), Y1092X (Bozon etal., pers. comm.), W1098R, M1101K (Zielenski et al., pers. comm.); Exon 18: D1152H (Highsmith et al., pers. comm.); Exon 19:R1162X (36), 3659delC (39), 3662delA (25), 3667del4 (Chillon et al., pers. comm.), 3737ddA (35), 3821ddT (15), I1234V (35), S1235R (31), Q1238X (26), 3849G-A (25), 385O-3T-G (38); Exon20:3860ins31 (Chillon etal., pers. comm.), S1255X (47), 3898insC (26), 3905insT (Malik et al., pers. comm.), D127ON (48), W1282X (49), Q1291R (Dork et al., pers. comm.), Exon 21: N1303H (35), N13O3K (50), W1316X (43); Exon 22: 11328L/4116delA (Dork and TQmmler, pers. comm.), E1371X (25); Exon 23: 4374+ 1G-T (38); Exon 24: 4382delA (Claustres et al., pers. comm.). Login to comment

PMID: 7513294 [PubMed] Culard JF et al: "Analysis of the whole CFTR coding regions and splice junctions in azoospermic men with congenital bilateral aplasia of epididymis or vas deferens."

No. Sentence Comment

27 The missense mutation A 1067T in exon 17b (Ferec et al. 1992) was identified in a CBAVD patient with AF508, but, interestingly, the familial study revealed that A1067T was located on the paternally inherited CF chromosome already bearing AF508. Login to comment
33 CFTR mutations identified in 12 patients lacking an epididymis or vas deferens Patient Age Mutations Exon XV2c/KM19 (years) haplotypesa CBAVD 1 43 Unknown B Unknown A CBAVD 6 33 p AF508/A1067T 10/17b B m Unknown A CBAVD 8 32 p Unknown A m AF508 10 B CBAVD 9 27 p R347H 7 C m AF508 10 B CBAVD 11 31 m Unknown D p 2184delA+A---~G at 2183 13 B CBAVD 12 30 Unknown B Unknown B CBAVD 13 32 p AF508 10 B m Unknown A CBAVD 14 AF508 10 B R347H 7 C CUAVD 4 35 m G542X 11 B p Unknown D CBAE 2 28 Unknown C Unknown D CBAE 7 34 p Unknown B m S1235R 19 A CBAE 10 30 Unknown B Unknown C CBAVD, Congenital bilateral aplasia of the vas deferens; CUAVD, congenital unilateral aplasia of the vas deferens; CBAE, congenital bilateral aplasia of the epididymis; p, paternal chromosome; m, maternal chromosome The four haplotypes defined by the CFTR-linked polymorphic restriction sites XV-2c and KM-19 are as follows: A, 1-1; B, -2; C, 2-1; D, 2-2 (the absence of the restriction site for each polymorphism is defined as allele "1", and the presence of the site as allele "2") Table . Login to comment

PMID: 7513293 [PubMed] Chillon M et al: "Analysis of the CFTR gene confirms the high genetic heterogeneity of the Spanish population: 43 mutations account for only 78% of CF chromosomes."

No. Sentence Comment

31 At present, we have not detected any Spanish CF chromosomes bearing any of the following mutations: 394delTA, Y122X, 556delA, 852de122, R347P, $492F, 1677delTA, V520F, Q552X, R553X, L559S, R560K, R560T, Y563N, P564H, 2043delG, 3320ins5, R1066H, A1067T, H1085R, 3732delA, 3737delA, I1234V, S1255P, 3898insC, Q1291H or 4005+ 1G---~A. Login to comment

PMID: 11448786 [PubMed] Wine JJ et al: "Cystic fibrosis: the 'bicarbonate before chloride' hypothesis."

No. Sentence Comment

52 Ion transport (% WT) 42 41 69 75 >100 >100 98 + 103 100 + + 120 Pancreatic sufficient Pancreatic insufficient Bicarbonate Chloride - intermediate Chloride - high Unknown WT D648V R117H R1070Q H949Y G551S H620Q I148T A1067T G178R G970R S1255P G1244E G551D G1349D 0 0.5 1 1.5 2 2.5 Current Biology ࢞F508 Dispatch R absence of the vas deferens [16]. Login to comment

PMID: 22973227 [PubMed] Patrick AE et al: "Development of CFTR Structure."

No. Sentence Comment

155 For instance, in the NBD-ICL4 interface, mutants in ICL4 including L1065P, R1066C, and A1067T alter trafficking and chloride channel function (Cotten et al., 1996; Seibert et al., 1996). Login to comment

PMID: 23891399 [PubMed] Van Goor F et al: "Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function."

No. Sentence Comment

44 None M1V A46D E56K P67L R74W G85E E92K D110E D110H R117C R117H E193K L206W R334W I336K T338I S341P R347H R347P R352Q A455E L467P S492F F508del V520F A559T R560S R560T A561E Y569D D579G R668C L927P S945L S977F L997F F1052V H1054D K1060T L1065P R1066C R1066H R1066M A1067T R1070Q R1070W F1074L L1077P H1085R M1101K D1152H S1235R D1270N N1303K 0 100 200 300 400 500 600 * * * CFTR Mutation mRNA (% Normal CFTR) Fig. 1. Login to comment
64 Mutant CFTR form CFTR processing Mature/total % Normal CFTR Normal 0.89 &#b1; 0.01 100.0 &#b1; 18.5 G85E -0.05 &#b1; 0.04 -1.0 &#b1; 0.9 R560S 0.00 &#b1; 0.00 0.0 &#b1; 0.0 R1066C 0.02 &#b1; 0.01 0.0 &#b1; 0.0 S492F 0.00 &#b1; 0.00 0.1 &#b1; 0.1 R560T 0.01 &#b1; 0.01 0.2 &#b1; 0.1 V520F 0.05 &#b1; 0.03 0.3 &#b1; 0.2 M1101K 0.05 &#b1; 0.03 0.3 &#b1; 0.1 A561E 0.08 &#b1; 0.04 0.5 &#b1; 0.2 R1066M 0.02 &#b1; 0.02 0.5 &#b1; 0.4 N1303K 0.02 &#b1; 0.02 0.5 &#b1; 0.3 A559T 0.16 &#b1; 0.09 0.6 &#b1; 0.2 M1V 0.06 &#b1; 0.06 0.7 &#b1; 0.6 Y569D 0.11 &#b1; 0.04 0.6 &#b1; 0.2 R1066H 0.08 &#b1; 0.02a 0.7 &#b1; 0.2a L1065P 0.05 &#b1; 0.05 1.0 &#b1; 0.8 L467P 0.10 &#b1; 0.07 1.2 &#b1; 0.8 L1077P 0.08 &#b1; 0.04 1.5 &#b1; 0.6 A46D 0.21 &#b1; 0.08 1.9 &#b1; 0.5a E92K 0.06 &#b1; 0.05 1.9 &#b1; 1.3 H1054D 0.09 &#b1; 0.04 1.9 &#b1; 0.8 F508del 0.09 &#b1; 0.02a 2.3 &#b1; 0.5a H1085R 0.06 &#b1; 0.01a 3.0 &#b1; 0.7a I336K 0.42 &#b1; 0.05a 6.5 &#b1; 0.7a L206W 0.35 &#b1; 0.10a 6.8 &#b1; 1.7a F1074L 0.52 &#b1; 0.03a 10.9 &#b1; 0.6a A455E 0.26 &#b1; 0.10a 11.5 &#b1; 2.5a E56K 0.29 &#b1; 0.04a 12.2 &#b1; 1.5a R347P 0.48 &#b1; 0.04a 14.6 &#b1; 1.8a R1070W 0.61 &#b1; 0.04a 16.3 &#b1; 0.6a P67L 0.36 &#b1; 0.04a 28.4 &#b1; 6.8a R1070Q 0.90 &#b1; 0.01a 29.5 &#b1; 1.4a S977F 0.97 &#b1; 0.01a 37.3 &#b1; 2.4a A1067T 0.78 &#b1; 0.03a 38.6 &#b1; 6.1a D579G 0.72 &#b1; 0.02a 39.3 &#b1; 3.1a D1270N 1.00 &#b1; 0.00a,c 40.7 &#b1; 1.2a S945L 0.65 &#b1; 0.04a 42.4 &#b1; 8.9a L927P 0.89 &#b1; 0.01a,b 43.5 &#b1; 2.5a,b R117C 0.87 &#b1; 0.02a,b 49.1 &#b1; 2.9a,b T338I 0.93 &#b1; 0.03a,b 54.2 &#b1; 3.7a,b L997F 0.90 &#b1; 0.04a,b 59.8 &#b1; 10.4a,b D110H 0.97 &#b1; 0.01a,b 60.6 &#b1; 1.5a,b S341P 0.79 &#b1; 0.02a 65.0 &#b1; 4.9a,b R668C 0.94 &#b1; 0.03a,b 68.5 &#b1; 1.9a,b R74W 0.78 &#b1; 0.01a 69.0 &#b1; 2.7a,b D110E 0.92 &#b1; 0.05a,b 87.5 &#b1; 9.5a,b R334W 0.91 &#b1; 0.05a,b 97.6 &#b1; 10.0a,b K1060T 0.87 &#b1; 0.02a,b 109.9 &#b1; 28.0a,b R347H 0.96 &#b1; 0.02a,c 120.7 &#b1; 2.8a,b S1235R 0.96 &#b1; 0.00a,c 139.0 &#b1; 9.0a,b E193K 0.84 &#b1; 0.02a,b 143.0 &#b1; 17.1a,b R117H 0.86 &#b1; 0.01a,b 164.5 &#b1; 34.2a,b R352Q 0.98 &#b1; 0.01a,b 179.9 &#b1; 8.0a,c F1052V 0.90 &#b1; 0.01a,b 189.9 &#b1; 33.1a,b D1152H 0.96 &#b1; 0.02a,c 312.0 &#b1; 45.5a,b Notes to Table 1: Quantification of steady-state CFTR maturation expressed as the mean (&#b1;SEM; n = 5-9) ratio of mature CFTR to total CFTR (immature plus mature) or level of mature mutant CFTR relative to mature normal-CFTR (% normal CFTR) in FRT cells individually expressing CFTR mutations. Login to comment
74 Because the level of CFTR mRNA was similar across the panel of cell lines tested, the range in baseline activity and ivacaftor response likely reflects the severity of the functional defect and/or the 0 50 100 150 200 S341P R347P L467P S492F A559T A561E Y569D L1065P R1066C R1066M L1077P M1101K N1303K R560S L927P R560T H1085R V520F E92K M1V F508del H1054D I336K A46D G85E R334W T338I R1066H R352Q R117C L206W R347H S977F S945L A455E F1074L E56K P67L R1070W D110H D579G D110E R1070Q L997F A1067T E193K R117H R74W K1060T R668C D1270N D1152H S1235R F1052V Baseline With ivacaftor * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Chloride transport (% Normal) Mutant CFTR form 0 100 200 300 400 S341P R347P L467P S492F A559T A561E Y569D L1065P R1066C R1066M L1077P M1101K N1303K R560S L927P R560T H1085R V520F E92K M1V F508del H1054D I336K A46D G85E R334W T338I R1066H R352Q R117C L206W R347H S977F S945L A455E F1074L P67L E56K R1070W D110H D579G D110E R1070Q L997F A1067T E193K R117H R74W K1060T R668C D1270N D1152H S1235R F1052V * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Mature CFTR (% Normal) Mutant CFTR form A B Fig. 2. Login to comment
82 Mutation Patientsa Chloride transport (bc;A/cm2 ) Chloride transport (% normal) EC50 Baseline With ivacaftor Baseline With ivacaftor Fold increase over baselineb Normal 204.5 &#b1; 33.3 301.3 &#b1; 33.8c 100.0 &#b1; 16.3 147.3 &#b1; 16.5c 1.5 266 &#b1; 42 G551D 1282 1.5 &#b1; 0.7 113.2 &#b1; 13.0c 1.0 &#b1; 0.5 55.3 &#b1; 6.3c 55.3 312 &#b1; 73 F1052V 12 177.3 &#b1; 13.7 410.2 &#b1; 11.3c 86.7 &#b1; 6.7 200.7 &#b1; 5.6c 2.3 177 &#b1; 14 S1235R ND 160.6 &#b1; 25.7 352.1 &#b1; 43.4c 78.5 &#b1; 12.6 172.2 &#b1; 21.2c 2.2 282 &#b1; 104 D1152H 185 117.3 &#b1; 23.0 282.7 &#b1; 46.9c 57.4 &#b1; 11.2 138.2 &#b1; 22.9c 2.4 178 &#b1; 67 D1270N 32 109.5 &#b1; 20.5 209.5 &#b1; 27.4c 53.6 &#b1; 10.0 102.4 &#b1; 13.4c 1.9 254 &#b1; 56 R668C 45 99.0 &#b1; 9.4 217.6 &#b1; 11.7c 48.4 &#b1; 4.6 106.4 &#b1; 5.7c 2.2 517 &#b1; 105 K1060T ND 89.0 &#b1; 9.8 236.4 &#b1; 20.3c 43.5 &#b1; 4.8 115.6 &#b1; 9.9c 2.7 131 &#b1; 73 R74W 25 86.8 &#b1; 26.9 199.1 &#b1; 16.8c 42.5 &#b1; 13.2 97.3 &#b1; 8.2c 2.3 162 &#b1; 17 R117H 739 67.2 &#b1; 13.3 274.1 &#b1; 32.2c 32.9 &#b1; 6.5 134.0 &#b1; 15.7c 4.1 151 &#b1; 14 E193K ND 62.2 &#b1; 9.8 379.1 &#b1; 1.1c 30.4 &#b1; 4.8 185.4 &#b1; 1.0c 6.1 240 &#b1; 20 A1067T ND 55.9 &#b1; 3.2 164.0 &#b1; 9.7c 27.3 &#b1; 1.6 80.2 &#b1; 4.7c 2.9 317 &#b1; 214 L997F 27 43.7 &#b1; 3.2 145.5 &#b1; 4.0c 21.4 &#b1; 1.6 71.2 &#b1; 2.0c 3.3 162 &#b1; 12 R1070Q 15 42.0 &#b1; 0.8 67.3 &#b1; 2.9c 20.6 &#b1; 0.4 32.9 &#b1; 1.4c 1.6 164 &#b1; 20 D110E ND 23.3 &#b1; 4.7 96.4 &#b1; 15.6c 11.4 &#b1; 2.3 47.1 &#b1; 7.6c 4.1 213 &#b1; 51 D579G 21 21.5 &#b1; 4.1 192.0 &#b1; 18.5c 10.5 &#b1; 2.0 93.9 &#b1; 9.0c 8.9 239 &#b1; 48 D110H 30 18.5 &#b1; 2.2 116.7 &#b1; 11.3c 9.1 &#b1; 1.1 57.1 &#b1; 5.5c 6.2 249 &#b1; 59 R1070W 13 16.6 &#b1; 2.6 102.1 &#b1; 3.1c 8.1 &#b1; 1.3 49.9 &#b1; 1.5c 6.2 158 &#b1; 48 P67L 53 16.0 &#b1; 6.7 88.7 &#b1; 15.7c 7.8 &#b1; 3.3 43.4 &#b1; 7.7c 5.6 195 &#b1; 40 E56K ND 15.8 &#b1; 3.1 63.6 &#b1; 4.4c 7.7 &#b1; 1.5 31.1 &#b1; 2.2c 4.0 123 &#b1; 33 F1074L ND 14.0 &#b1; 3.4 43.5 &#b1; 5.4c 6.9 &#b1; 1.6 21.3 &#b1; 2.6c 3.1 141 &#b1; 19 A455E 120 12.9 &#b1; 2.6 36.4 &#b1; 2.5c 6.3 &#b1; 1.2 17.8 &#b1; 1.2c 2.8 170 &#b1; 44 S945L 63 12.3 &#b1; 3.9 154.9 &#b1; 47.6c 6.0 &#b1; 1.9 75.8 &#b1; 23.3c 12.6 181 &#b1; 36 S977F 9 11.3 &#b1; 6.2 42.5 &#b1; 19.1c 5.5 &#b1; 3.0 20.8 &#b1; 9.3c 3.8 283 &#b1; 36 R347H 65 10.9 &#b1; 3.3 106.3 &#b1; 7.6c 5.3 &#b1; 1.6 52.0 &#b1; 3.7c 9.8 280 &#b1; 35 L206W 81 10.3 &#b1; 1.7 36.4 &#b1; 2.8c 5.0 &#b1; 0.8 17.8 &#b1; 1.4c 3.6 101 &#b1; 13 R117C 61 5.8 &#b1; 1.5 33.7 &#b1; 7.8c 2.9 &#b1; 0.7 16.5 &#b1; 3.8c 5.7 380 &#b1; 136 R352Q 46 5.5 &#b1; 1.0 84.5 &#b1; 7.8c 2.7 &#b1; 0.5 41.3 &#b1; 3.8c 15.2 287 &#b1; 75 R1066H 29 3.0 &#b1; 0.3 8.0 &#b1; 0.8c 1.5 &#b1; 0.1 3.9 &#b1; 0.4c 2.6 390 &#b1; 179 T338I 54 2.9 &#b1; 0.8 16.1 &#b1; 2.4c 1.4 &#b1; 0.4 7.9 &#b1; 1.2c 5.6 334 &#b1; 38 R334W 150 2.6 &#b1; 0.5 10.0 &#b1; 1.4c 1.3 &#b1; 0.2 4.9 &#b1; 0.7c 3.8 259 &#b1; 103 G85E 262 1.6 &#b1; 1.0 1.5 &#b1; 1.2 0.8 &#b1; 0.5 0.7 &#b1; 0.6 NS NS A46D ND 2.0 &#b1; 0.6 1.1 &#b1; 1.1 1.0 &#b1; 0.3 0.5 &#b1; 0.6 NS NS I336K 29 1.8 &#b1; 0.2 7.4 &#b1; 0.1c 0.9 &#b1; 0.1 3.6 &#b1; 0.1c 4 735 &#b1; 204 H1054D ND 1.7 &#b1; 0.3 8.7 &#b1; 0.3c 0.8 &#b1; 0.1 4.2 &#b1; 0.1c 5.3 187 &#b1; 20 F508del 29,018 0.8 &#b1; 0.6 12.1 &#b1; 1.7c 0.4 &#b1; 0.3 5.9 &#b1; 0.8c 14.8 129 &#b1; 38 M1V 9 0.7 &#b1; 1.4 6.5 &#b1; 1.9c 0.4 &#b1; 0.7 3.2 &#b1; 0.9c 8.0 183 &#b1; 85 E92K 14 0.6 &#b1; 0.2 4.3 &#b1; 0.8c 0.3 &#b1; 0.1 2.1 &#b1; 0.4c 7.0 198 &#b1; 46 V520F 58 0.4 &#b1; 0.2 0.5 &#b1; 0.2 0.2 &#b1; 0.1 0.2 &#b1; 0.1 NS NS H1085R ND 0.3 &#b1; 0.2 2.1 &#b1; 0.4 0.2 &#b1; 0.1 1.0 &#b1; 0.2 NS NS R560T 180 0.3 &#b1; 0.3 0.5 &#b1; 0.5 0.1 &#b1; 0.1 0.2 &#b1; 0.2 NS NS L927P 15 0.2 &#b1; 0.1 10.7 &#b1; 1.7c 0.1 &#b1; 0.1 5.2 &#b1; 0.8c 52.0 313 &#b1; 66 R560S ND 0.0 &#b1; 0.1 -0.2 &#b1; 0.2 0.0 &#b1; 0.0 -0.1 &#b1; 0.1 NS NS N1303K 1161 0.0 &#b1; 0.0 1.7 &#b1; 0.3 0.0 &#b1; 0.0 0.8 &#b1; 0.2 NS NS M1101K 79 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 NS NS L1077P 42 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 NS NS R1066M ND 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 NS NS R1066C 100 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 NS NS L1065P 25 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 NS NS Y569D 9 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 NS NS A561E ND 0.0 &#b1; 0.1 0.0 &#b1; 0.1 0.0 &#b1; 0.0 0.0 &#b1; 0.1 NS NS A559T 43 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 NS NS S492F 16 0.0 &#b1; 0.0 1.7 &#b1; 1.2 0.0 &#b1; 0.0 0.8 &#b1; 0.6 NS NS L467P 16 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 NS NS R347P 214 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 0.0 &#b1; 0.0 NS NS S341P 9 0.0 &#b1; 0.0 0.2 &#b1; 0.2 0.0 &#b1; 0.0 0.1 &#b1; 0.1 NS NS a Number of individuals with the individual mutation in the CFTR-2 database (www.CFTR2.org). Login to comment
86 For example, the baseline level of chloride transport and ivacaftor response was higher for mutant CFTR forms associated with mild defects in CFTR processing (e.g., E56K, P67L, L206W, A455E, D579G, S945L, S977F, A1067T, R1070Q, R1070W, F1074L, and D1270N) than for those associated with severe defects in CFTR processing (e.g., F508del, H1054D, R1066H). Login to comment
89 For mutant CFTR forms that have multiple defects (e.g., R117H, F508del, S945L, R1070Q, A1067T, R1070W, and R347P), the relative impact of each defect is likely to affect the magnitude of the baseline chloride transport and ivacaftor response in vitro and in a clinical setting. Login to comment
92 Mutant CFTR forms that did not significantly respond to ivacaftor under the experimental conditions used in this study were generally associated with severe defects in CFTR processing A B C D E F 0 100 200 300 400 -9 -8 -7 -6 -5 -4 0 S1235R D1152H F1052V D1270N ivacaftor [Log M] 0 100 200 300 400 -9 -8 -7 -6 -5 -4 0 R668C K1060T R74W R117H ivacaftor [Log M] 0 100 200 300 400 -9 -8 -7 -6 -5 -4 0 E193K A1067T L997F R1070Q ivacaftor [Log M] Chloride Transport ( &#b5;A/cm 2 ) Chloride Transport ( &#b5;A/cm 2 ) Chloride Transport ( &#b5;A/cm 2 ) Chloride Transport ( &#b5;A/cm 2 ) Chloride Transport ( &#b5;A/cm 2 ) Chloride Transport ( &#b5;A/cm 2 ) Chloride Transport ( &#b5;A/cm 2 ) Chloride Transport ( &#b5;A/cm 2 ) Chloride Transport ( &#b5;A/cm 2 ) 0 100 200 300 400 -9 -8 -7 -6 -5 -4 0 D110E D579G D110H R1070W ivacaftor [Log M] 0 100 200 300 400 -9 -8 -7 -6 -5 -4 0 F1074L E56K P67L A455E ivacaftor [Log M] 0 100 200 300 400 -9 -8 -7 -6 -5 -4 0 R347H S945L L206W S977F ivacaftor [Log M] 0 100 200 300 400 -8 -6 -4 0 T338I R1066H R117C R352Q ivacaftor [Log M] 0 100 200 300 400 -9 -8 -7 -6 -5 -4 0 F508del R334W H1054D E92K ivacaftor [Log M] 0 5 10 15 20 -9 -8 -7 -6 -5 -4 0 F508del R334W H1054D E92K R1066H T338I ivacaftor [Log M] G H I Fig. 3. Login to comment

PMID: 24727426 [PubMed] Wang Y et al: "Understanding how cystic fibrosis mutations disrupt CFTR function: from single molecules to animal models."

No. Sentence Comment

1987 Encouragingly, the data suggest that ivacaftor potentiates multiple gating mutants located in different parts of CFTR structure including R117H (M2), R668C (RD) and A1067T (ICL4) (Yu et al., 2012; Van Goor et al., 2014). Login to comment