ABCMdb

PMID: 11938439

Audrezet MP, Chen JM, Le Marechal C, Ruszniewski P, Robaszkiewicz M, Raguenes O, Quere I, Scotet V, Ferec C
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.
Eur J Hum Genet. 2002 Feb;10(2):100-6., [PubMed]

Sentences

No. Mutations Sentence Comment

38 ABCC7 p.Arg117His Only the known c.365G4A (CGC4CAC; R122H, originally termed R117H in the chymotrypsin numbering system5,24 ) mutation was found in a 42-year-old male subject (Table 1). Login to comment 48 ABCC7 p.Gln1476* However, a sweat test done retrospectively was positive in two of them, at 90 mmol/L for the patient with a F508del/P5L genotype and at 80 mmol/L for the patient with a F508del/Q1476X genotype. Login to comment 56 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg352Gln ABCC7 p.Glu217Gly ABCC7 p.Leu967Ser ABCC7 p.Gln1476* ABCC7 p.Val562Ile ABCC7 p.Ala1136Thr `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. Login to comment 72 ABCC7 p.Arg117His Additionally, none of the genotyped F508del and R117H mutations were found in 14 Japanese patients with ICP,14 a not surprising result given that these alleles are extremely rare in the Japanese population. Login to comment 85 ABCC7 p.Arg352Gln ABCC7 p.Glu217Gly ABCC7 p.Leu967Ser ABCC7 p.Val562Ile ABCC7 p.Ala1136Thr Firstly, we found a total of 10 additional alleles (R352Q, P5L, c.4575+2G4A, V562I, IVS3-6T4C, E217G/A1136T, IVS18-20T4C, and L967S; Table 1) that would have been missed by the conventional genotyping method. Login to comment 87 ABCC7 p.Arg352Gln ABCC7 p.Ala1136Thr For example, R352Q, P5L, and A1136T occur in strictly conserved residues (refer to Figure 2 in Chen et al33 ). Login to comment 88 ABCC7 p.Arg352Gln ABCC7 p.Gln1476* ABCC7 p.Ala1136Thr In particular, R352Q is within the stringently conserved motif T351-R352- Q353, which is immediately downstream of TM6 and has been suggested to loop back into the chloride channel, narrowing the lumen and thereby forming both the major resistance to current flow and the anion selectivity filter;34 A1136T is within TM12; c.4575+2G4A, occurring just two nucleotides downstream of the translation stop codon, may affect the interplay between splicing and polyadenylation or alter the mRNA stability; Q1476X is a nonsense mutation. Login to comment 91 ABCC7 p.Gln1476* Although a sweat test was positive in the patients (both were males) with F508del/P5L (90 mmol/l) and F508del/Q1476X (80 mmol/ l), neither of them showed evidence of CF-related lung disease. Login to comment 93 ABCC7 p.Arg75Gln ABCC7 p.Ile336Lys Thus, as in the case of the two previously reported compound heterozygotes, F508del/R117H4 and I336K/R75Q,32 none of our four compound heterozygotes could be described as carrying two `severe' CFTR mutations. Login to comment 94 ABCC7 p.Gln1476* ABCC7 p.Gln1476* Still, one may argue that the F508del/Q1476X genotype represents two `severe' alleles, since Q1476X is an obvious nonsense mutation resulting in a truncation of the last four amino acids of the CFTR protein. Login to comment 96 ABCC7 p.Gln1476* One may also argue that the two patients with the F508del/ P5L (90 mmol/l) and F508del/Q1476X (80 mmol/l) genotypes had, in fact, typical CF disease, according to the diagnostic criteria established by a consensus panel of the Cystic Fibrosis Foundation.35 Regarding this issue, we agree with the view that `we need to have both a CF `disease' and a CF `syndrome'. Login to comment 103 ABCC7 p.Arg553* ABCC7 p.Gln493* In this regard, a F508del/5T genotype was identified three times3,4 and Q493X/5T3 and R553X/5T3 once each in patients with ICP. Login to comment 104 ABCC7 p.Trp1282* In this study, the 5T allele was found in a patient having the W1282X mutation (Table 1). Login to comment