ABCMdb

PMID: 14586256

Reboul MP, Laharie D, Amouretti M, Lacombe D, Iron A
Isolated idiopathic chronic pancreatitis associated with a compound heterozygosity for two mutations of the CFTR gene.
Gastroenterol Clin Biol. 2003 Aug-Sep;27(8-9):821-4., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCC7 p.Gly542* ABCC7 p.Ser1235Arg SUMMARY We report the case of a patient suffering from idiopathic chronic pancreatitis (ICP) and compound heterozygous for mutations G542X and S1235R of the cystic fibrosis transmembrane regulator (CFTR) gene. Login to comment 3 ABCC7 p.Gly542* G542X is a severe mutation, which is usually found in classical cystic fibrosis when associated with other severe mutations. Login to comment 4 ABCC7 p.Ser1235Arg S1235R is a quite rare abnormality recently reported as being potentially pathogenic when combined in trans with a second CF mutation. Login to comment 6 ABCC7 p.Gly542* ABCC7 p.Ser1235Arg The history and the clinical features of our patient indicate an unambiguous isolated ICP in which the presence of the S1235R mutation - in trans with regard to G542X - is likely responsible for the ICP phenotype. Login to comment 8 ABCC7 p.Gly542* ABCC7 p.Ser1235Arg RE´SUME´ Pancréatite chronique idiopathique isolée associée à une hétérozygotie composite pour deux mutations du gène CFTR Marie-Pierre REBOUL, David LAHARIE, Michel AMOURETTI, Didier LACOMBE, Albert IRON (Gastroenterol Clin Biol 2003;27:821-824) Nous rapportons le cas d`un malade souffrant de pancréatite chronique idiopathique (PCI) hétérozygote composite pour les mutations G542X et S1235R du gène CFTR. Login to comment 10 ABCC7 p.Gly542* G542X est une mutation sévère rencontrée assez fréquemment - en association avec d`autres mutations sévères - dans des formes de mucoviscidose classique. Login to comment 11 ABCC7 p.Ser1235Arg S1235R est une anomalie assez rare, rapportée récemment comme étant potentiellement délétère quand elle est associée en trans à une autre mutation du gène CFTR. Login to comment 13 ABCC7 p.Gly542* ABCC7 p.Ser1235Arg L`histoire et le tableau clinique de la maladie chez notre malade évoquent de manière complète et sans ambiguïté une PCI isolée dans laquelle la présence de la mutation S1235R - en position trans par rapport à G542X - est très vraisemblablement responsable du phénotype de pancréatite chronique idiopathique. Login to comment 23 ABCC7 p.Gly542* ABCC7 p.Ser1235Arg He had an original compound heterozygosity for the severe G542X mutation and the mild S1235R mutation. Login to comment 44 ABCC7 p.Gly542* This revealed the G542X mutation with a heterozygous status. Login to comment 46 ABCC7 p.Ser1235Arg This revealed the presence of the S1235R mutation in exon 19 (T>G at nucleotide 3837). Login to comment 59 ABCC7 p.Arg117His Patients no 1 and no 8 bear a CBAVD and the R117H mutation which is very often responsible for this CFTR pathology. Login to comment 60 ABCC7 p.Arg117His ABCC7 p.Asn1303Lys Patient no 2 is a compound heterozygote for R117H and N1303K: her phenotype is that of a moderate cystic fibrosis as shown by respiratory signs and an abnormal nasal potential difference in the context of a borderline sweat test. Login to comment 62 ABCC7 p.Arg75Gln Patient no 4 is debatable from two points of view: a) her status of compound heterozygote for two mutations of the CFTR gene including one (R75Q) considered by some as a simple polymorphism [14], and by others as a mild mutation [15]; b) her clinical features of pancreatic damage and nasal polyps. Login to comment 67 ABCC7 p.Gly542* ABCC7 p.Ser1235Arg ABCC7 p.Asp1152His ABCC7 p.Leu997Phe ABCC7 p.Ile1027Thr In five patients (no 5, 9, 10, 11, 15) who bear a frequent mutation well known for its severity (F508del or G542X), the involvement of the ICP phenotype could lie in their "second" missense mutation, i.e. L997F in exon 17b (Patient no 5), I1027T in exon 17a (Patient no 9), D1152H in exon 18 (Patients no 10 and 11) and S1235R in exon 19 (Patient no 15); and the presence of 2 of these 4 missense mutations in patient no 7 could actually strengthen this hypothesis but to date little is known about the possible impact of his 5T allele on the phenotype (possible sterility). Login to comment 72 ABCC7 p.Gly1069Arg It is also the case for the 2 CF mutated alleles 3120G>A in exon 16 (patient no 13) and G1069R in exon 17b (patient 14), but we have no information about the presence or absence of other clinical features these patients could present. Login to comment 74 ABCC7 p.Ser1235Arg Particular interest should be paid to the S1235R mutation of our patient. Login to comment 75 ABCC7 p.Gly542* ABCC7 p.Ser1235Arg It is a rare moderate mutation recently studied by Cuppens`s team [16] who showed that the deleterious character Fig. 2 - Pedigree of the family (limited to the subjects investigated) with mention of the haplotypes IVS8CA-TGm-Tn-M470V-IVS17bTA-IVS17bCA and the presence or absence (-) of the 2 familial mutations G542X (exon 10) and S1235R (exon 19). Login to comment 76 ABCC7 p.Gly542* ABCC7 p.Ser1235Arg ↑ proband Arbre généalogique de la famille (limité aux sujets analysés) avec mention des haplotypes IVS8CA-TGm-Tn-M470V-IVS17bTA-IVS17bCA et de la présence ou de l`absence (-) des 2 mutations familiales G542X (exon 10) et S1235R (exon 19). Login to comment 80 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Ser1235Arg ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Ile1027Thr ABCC7 p.Ile336Lys ABCC7 p.Gly1069Arg Patient CFTR no PolyT genotype Sex genotype Age (years) Sweat chloride (mmol/L) Anamnestic features known to be associated with atypical CF Reference 1 F508del/R117H 9T/7T M 45 29 CBAVD [4] 2 N1303K/R117H 9T/7T F n.a. 37 bronchiectasis, sinusitis, positive NPD [5] 3 R1162X/2789+5G>A 7T/7T F n.a. 108 chronic cough [5] 4 I336K/R75Q 7T/7T F 26 26 nasal polyposis [7] 5 F508del/L997F 9T/7T M 17 24 none [11] 6 3849+10kbC>T/3878delG 7T/7T M 14 n.a. none [11] 7 S1235R/L997F 5T/7T M 27 25 none [11] 8 F508del/R117H n.a. M 45 29 CBAVD, smooth P. aeruginosa [12] 9 F508del/I1027T n.a. F 32 59 none [12] 10 F508del/D1152H n.a. M 8 62 none [12] 11 F508del/D1152H n.a. F 15 32 none [12] 12 F508del/P574H n.a. F 26 81 sinus surgery, S. aureus, S. maltophilia [12] 13 F508del/3120G>A n.a. F 40 n.a. n.a. [12] 14 F508del/G1069R n.a. M 16 n.a. n.a. [12] 15 G542X/S1235R 7T/7T M 35 15 none [this study] n.a.: not available. Login to comment 86 ABCC7 p.Ser1235Arg At the same time, Monaghan et al. [17] considered that S1235R - when combined with a second CF mutation - may be pathogenic. Login to comment 87 ABCC7 p.Ser1235Arg In conclusion, among the 7 PCI patients so far reported as compound heterozygous for two mutations of the CFTR gene and bearers of a pathology limited to the pancreas, our patient, with his detailed clinical investigation showing the isolated nature of the pancreas damage, could be one of the most interesting cases of compound heterozygosity for two mutations of the CFTR gene, including one (S1235R), which is not very common in the different forms of cystic fibrosis. Login to comment 90 ABCC7 p.Ser1235Arg If so, this would deprive us of information about rare mutations which - like the S1235R mutation in the patient reported here - could explain more specifically the ICP phenotype. Login to comment