ABCMdb

PMID: 12127423

Girodon E, Sternberg D, Chazouilleres O, Cazeneuve C, Huot D, Calmus Y, Poupon R, Goossens M, Housset C
Cystic fibrosis transmembrane conductance regulator (CFTR) gene defects in patients with primary sclerosing cholangitis.
J Hepatol. 2002 Aug;37(2):192-7., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCC7 p.Asp1270Asn ABCC7 p.Ser1235Arg ABCC7 p.Leu997Phe ABCC7 p.Asn782Lys Results: Four patients (13.8%) were heterozygous for a CFTR mutation, including a new putative severe CF-causing mutation (N782K), and three mild defects (L997F, D1270N, and S1235R). Login to comment 72 ABCC7 p.Asp1270Asn ABCC7 p.Ser1235Arg ABCC7 p.Leu997Phe ABCC7 p.Asn782Lys Four patients (13.8%) were heterozygous for one of the following CFTR mutations: N782K, L997F, S1235R and D1270N. Login to comment 73 ABCC7 p.Asp1270Asn ABCC7 p.Ser1235Arg ABCC7 p.Leu997Phe L997F [14,15], S1235R [40,41], and D1270N [42,43] have been previously described as mild mutations. Login to comment 74 ABCC7 p.Asp1270Asn ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Leu997Phe ABCC7 p.Asn782Lys ABCC7 p.Asn782Lys N782K, a new missense mutation (C-to-A transversion at nucleotide 2478), is located in exon 13, generates an ApoI restriction site, and putatively E. Girodon et al. / Journal of Hepatology 37 (2002) 192-197 193 E.Girodonetal./JournalofHepatology37(2002)192-197194 Table 1 Clinical status and CFTR genotype in PSC patientsa Patient Gender Age (years) at onset IBD Episode(s) of acute cholangitis Cirrhosis and/or portal hypertension Cholangiocarcinoma Liver transplantation CFTR mutations TGmTn genotype Other sequence variations 1 F 37 UC Yes Yes Yes (67) No N782K/- 12-7/11-7 M470V 2 M 8 No No Yes No Yes (18) D1270N/- 11-9/11-7 M470V 3 M 27 No Yes No No No L997F/- 11-7/11-7 V470V 4 M 58 Crohn Yes No No Yes (65) S1235R/- 11-7/12-7 M470V 5 F 17 Unclassified No No No No 10-7/11-5 M470M 6 F 43 Crohn Yes Yes No Yes (46) 10-7/11-5 M470M 7 F 58 UC Yes Yes Yes (58) No 10-7/11-7 M470V,R75Q,406-13T/C 8 M 32 Crohn Yes Yes No Yes (38) 11-7/11-7 V470V, R75Q 9 F 41 UC No No No Yes (48) 10-7/11-7 M470V, 1716G/A 10 M 23 No No No No No 12-7/10-7 M470M, 1715-12T/C 11 F 55 Crohn No No No No 11-9/12-7 M470M 12 M 39 Unclassified Yes No No No 10-7/11-7 M470M 13 M 45 No No No No No 9-9/11-7 M470V 14 M 23 UC No No No Yes (23) 10-9/11-7 M470M 15 M 20 No Yes Yes No Yes (29) 10-9/10-7 M470M 16 M 17 Crohn No Yes No Yes (47) 11-9/11-7 M470V 17 M 43 Unclassified Yes No No No 11-9/11-7 M470V 18 M 47 No No No No No 11-9/10-7 M470M 19 M 42 Crohn Yes No No No 11-7/11-7 V470V 20 M 31 Crohn Yes No No Yes (34) 10-7/11-7 M470V 21 M 16 Crohn No No No No 10-7/12-7 M470V 22 M 56 No Yes Yes No No 11-7/11-7 V470V 23 F 47 No Yes No Yes (54) No 11-7/12-7 M470V 24 F 19 Crohn No No Yes (29) No 10-7/12-7 M470M 25 M 35 UC Yes No No No 11-7/12-7 M470V 26 M 31 UC No Yes Yes (45) Yes (45) 11-7/12-7 V470V 27 F 52 Crohn Yes Yes No Yes (56) 10-7/11-7 M470V 28 F 55 Crohn No No No No 10-9/11-7 M470V 29 F 43 NA No No Yes (43) No 11-7/11-7 V470V a IBD, inflammatory bowel disease; UC, ulcerative colitis; NA, non-available; and age (years) at diagnosis of cholangicarcinoma or at liver transplantation is indicated within brackets. Login to comment 78 ABCC7 p.Arg117His ABCC7 p.Arg347His ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala Four additional subjects (3.5%) carried one of the following mild defects: R117H, R347H, R74W-D1270N and R668C-G576A. Login to comment 80 ABCC7 p.Arg75Gln Some are indicated in Table 1 (M470V, R75Q, 1716G/A), as they possibly alter in a minor fashion the CFTR protein function [45-47]. Login to comment 92 ABCC7 p.Asn782Lys One of these mutations, N782K, is a new missense mutation, that we never observed in more than 1000 non-CF chromosomes. Login to comment 94 ABCC7 p.Asn782Lys We would therefore postulate that N782K is a severe CF-causing defect. Login to comment 96 ABCC7 p.Asp1270Asn The D1270N mutation, described in patients with CBAVD or mild CF, is classified as a mild defect upon results of functional studies [42]. Login to comment 97 ABCC7 p.Leu997Phe The L997F mutation was initially reported as a polymorphism since it was observed on the non-CF chromosome of a healthy CF carrier [28]. Login to comment 99 ABCC7 p.Ser1235Arg ABCC7 p.Gly628Arg S1235R was first reported in a severely affected CF patient, who also carried the G628R mutation on the same allele [40]. Login to comment 100 ABCC7 p.Ser1235Arg ABCC7 p.Gly628Arg S1235R was subsequently detected without G628R in CF patients [32], in patients with CBAVD [12,49], and even in female healthy CF carriers (Claustres, Fe´rec, personal communications), but not in fertile male CF carriers. Login to comment 102 ABCC7 p.Ser1235Arg In particular, it has been suggested that the presence of IVS8-5T splicing variant in cis has a deleterious influence on the outcome of the S1235R mutation [32]. Login to comment 103 ABCC7 p.Ser1235Arg However, the S1235R mutation has also been detected in CF patients, without IVS8-5T or any other detectable variant in cis. Login to comment 104 ABCC7 p.Ser1235Arg It is assumed that the S1235R mutation alters interactions of CFTR with other proteins rather than chloride ion transport which is maintained in cells transfected with the R1235 mutant [41]. Login to comment 107 ABCC7 p.Arg75Gln However, the latter mutations included the R75Q variation and other conservative missense mutations which cannot be defined as polymorphisms on the basis of their frequency while their deleterious effect on CFTR function is disputable. Login to comment