ABCMdb

PMID: 12865275

Ahmed N, Corey M, Forstner G, Zielenski J, Tsui LC, Ellis L, Tullis E, Durie P
Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas.
Gut. 2003 Aug;52(8):1159-64., [PubMed]

Sentences

No. Mutations Sentence Comment

130 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Gly542* The most common mutation was ∆F508 (71.3%) followed by G551D (2.9%), G542X (2.3%), 621+1G→T (1.2%), and W1282X (1.2%). Login to comment 143 ABCC7 p.Arg117His For example, R117H was noted to be present in PS patients and therefore an assumption was made that this was a mild mutation.9 From these studies it was determined that most individuals with PI have two severe CFTR mutations while those with the PS phenotype have one or two mild mutations. Login to comment 279 ABCC7 p.Gly542* For example, a patient carrying a class I mutation (for example, G542X) in combination with ∆F508 (class II) was classified as class I although the genotype is in fact a compound heterozygote of class I/II. Login to comment 293 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Gly542* The most common mutations were: ∆F508 (in 943 chromosomes, 71.2%), G551D (39, 2.9%), G542X (31, 2.3%), 621+1G→T, W1282X (16, 1.2%), and R117H (11, 0.8%). Login to comment 294 ABCC7 p.Ala455Glu ABCC7 p.Arg334Trp ABCC7 p.Arg1162* ABCC7 p.Val520Phe ABCC7 p.Gly85Glu ABCC7 p.Tyr1092* Less common mutations included G85E and 5T (n=5 chromosomes), A455E and R1162X (n=4 chromosomes), R347, Y1092X, R334W, and V520F (n=3 chromosomes). Login to comment 307 ABCC7 p.Gly85Glu This includes one patient who carries the missense mutation G85E which appears to have an indeterminate effect on pancreatic phenotype as it has been observed in patients with PS and PI phenotypes.23 All but one of 49 individuals carrying at least one mutation belonging to classes IV or V have remained PS. Login to comment 308 ABCC7 p.Ile1234Val The exception, a patient with the class IV mutation I1234V, developed PI at the age of 25 years, after symptoms of chronic pancreatitis lasting 10 years. Login to comment 309 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Ser1251Asn ABCC7 p.Glu585* ABCC7 p.Gln493* ABCC7 p.Arg560Thr ABCC7 p.Arg560Thr ABCC7 p.Arg75Gln ABCC7 p.Pro67Leu ABCC7 p.Tyr1092* ABCC7 p.Ile1234Val ABCC7 p.Leu1077Pro ABCC7 p.Glu60* ABCC7 p.Ala559Thr ABCC7 p.Asp614Gly ABCC7 p.Leu1335Pro ABCC7 p.Glu1104* ABCC7 p.His199Arg 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. Login to comment 322 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Gly542* The four next most common mutations reported in this study (G551D, G542X, 621+1G→T, and W1282X) each accounted for Table 3 Pancreatic ductular and acinar secretion classified according to the functional consequences of CFTR gene mutations Functional class n Ductular function Acinar function Fluid† (ml/kg/h) Bicarbonate‡ (mmol/kg/h) Chloride‡ (mmol/kg/h) Trypsin* (U/kg/h) Colipase* (U/kg/h) Total lipase* (U/kg/h) Class I 7 2.3 (1.5) 0.03 (0.02) 0.15 (0.14) 19 (42) 142 (201) 290 (388) Class II 33 2.9 (2.4) 0.04 (0.04) 0.21 (0.33) 31 (63) 111 (197) 202 (276) Class III 6 1.1 (0.87) 0.02 (0.02) 0.12 (0.07) 109 (256) 235 (483) 608 (1280) Class IV 14 4.0 (2.8) 0.19 (0.2) 0.32 (0.12) 1032 (768) 9840 (10698) 12563 (10461) Class V 10 4.8 (3.2) 0.12 (0.07) 0.36 (0.23) 1535 (1406) 12161 (13550) 16449 (15482) Control 21 10.0 (3.9) 0.57 (0.22) 0.62 (0.3) 2291 (836) 13036 (5958) 19767 (8623) Values are mean (SD). Login to comment 364 ABCC7 p.Gly85Glu A small number of mutations (for example, G85E) are considered to be indeterminate due to their inconsistent effect on pancreatic phenotype. Login to comment