ABCMdb

PMID: 9630075

Arduino C, Ferrone M, Brusco A, Garnerone S, Fontana D, Rolle L, Carbonara AO
Congenital bilateral absence of vas deferens with a new missense mutation (P499A) in the CFTR gene.
Clin Genet. 1998 Mar;53(3):202-4., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Pro499Ala missense the CFTR gene mutation Arduino C, Ferrone M, Brusco A, Garnerone S, Fontana D, Rolle L, Carbonara AO.Congenital bilateral absence of vas deferens with a new missense mutation (P499A)in the CFTR gene. Login to comment 4 ABCC7 p.Trp1282* ABCC7 p.Pro499Ala ABCC7 p.Pro499Ala 0 Munksgaard, 1998 We describe a congenital bilateral absence of the vas deferens (CBAVD) patient with a compound heterozygosity in the cystic fibrosis transmembrane regulator ( C n R ) gene for a stop mutation W1282X and a new missense mutation P499A.The P499A is interpreted as a mild mutation whose phenotypic effects, in this case limited to the development of wolffian duct derivatives,are revealed only in combination with a severe CFTR mutation. Login to comment 11 ABCC7 p.Trp1282* ABCC7 p.Pro499Ala The present study reports a CBAVD patient with a compound heterozygosity in the CFTR gene for a stop mutation (W1282X) and a new missense mutation (P499A). Login to comment 12 ABCC7 p.Pro499Ala The effects of this genotype are 202 (P499A) in C Arduino., M Ferroneb, A Bruscob,S Gameroneb, D Fontaria', L Rolledand A 0 Carbonarab a servizioUniversitario Convenzionato di Genetica Medica. Login to comment 31 ABCC7 p.Pro499Ala P499A and W1289X mutations are also included. Login to comment 34 ABCC7 p.Pro499Ala The wild type allele produced three fragments of 257, 223 and 11 bp; the P499A mutations yielded two fragments of 257 and 234 bp. Login to comment 39 ABCC7 p.Pro499Ala ABCC7 p.Pro499Ala Results Patient SA analysed for the 12 CF mutations proved positive for W128X, which was inherited from the mother (1-2), Direct sequencing of exon 10, which displayed a band shift, showed C-.G transversion at position 1627 that changed residue 499 from Pro to Ala (P499A). Login to comment 41 ABCC7 p.Pro499Ala The P499A was inherited from the father (1-1) and it is also present in the sister (11-3). Login to comment 42 ABCC7 p.Trp1282* ABCC7 p.Pro499Ala The P499A behaves as allelic to W1282X. Login to comment 44 ABCC7 p.Pro499Ala Fig. la displays the haplotypes deduced from the segregation of six CFTR-linked Arduino et al. polymorphic sites; note that the 5T variant and P499A are in trans in 1-1. Login to comment 45 ABCC7 p.Pro499Ala Screening of 200 normal chromosomes from healthy individuals detected the new P499A mutation in two subjects YO). Login to comment 46 ABCC7 p.Pro499Ala None of the 105 CF uncharacterised chromosomes carried the P499A. Login to comment 49 ABCC7 p.Trp1282* ABCC7 p.Pro499Ala The CFTR genotype of our patient is represented by a severe mutation (W1282X) and by a new missense substitution P499A. Login to comment 50 ABCC7 p.Pro499Ala Several considerations suggest that P499A is not a neutral polymorphic variant but a mild mutation that in the context of a peculiar CFTR genotype can be associated with CBAVD. Login to comment 52 ABCC7 p.Pro574His ABCC7 p.Ala455Glu ABCC7 p.Ser549Asn ABCC7 p.Gly576Ala Other missense mutations in this domain (A455E, P574H, G576A, S549N) have been found associated with a mild CF phenotype and their functional analysis in transfected cells revealed a low transport efficiency of the chloride channel and a reduced protein expression at the apical cell surface, which can explain the mild clinical phenotype (6). Login to comment 53 ABCC7 p.Pro499Ala ABCC7 p.Pro499Ala In comparison with these mutants, P499A appears even milder; indeed the patient`s healthy father carries P499A in one chromosome and the 5T allele in the other without showing any sign of CFTR dysfunction. Login to comment 54 ABCC7 p.Pro499Ala This interpretation is also substantiated by the absence of P499A on 306 CF chromosomes. Login to comment 55 ABCC7 p.Pro499Ala In conclusion, P499A appears to belong to the category of substitutions that slightly affect the CFTR function and can therefore give rise to a mild phenotype such as CBAVD only in combination with a severe mutation. Login to comment