ABCMdb

PMID: 15705389

Grangeia A, Carvalho F, Fernandes S, Silva J, Sousa M, Barros A
A novel missense mutation P1290S at exon-20 of the CFTR gene in a Portuguese patient with congenital bilateral absence of the vas deferens.
Fertil Steril. 2005 Feb;83(2):448-51., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Pro1290Ser A novel missense mutation P1290S at exon-20 of the CFTR gene in a Portuguese patient with congenital bilateral absence of the vas deferens Ana Grangeia, B.Sc.,a Filipa Carvalho, Ph.D.,a Susana Fernandes, Ph.D.,a Joaquina Silva, M.D.,b Mário Sousa, M.D., Ph.D.,a,b,c and Alberto Barros, M.D., Ph.D.a,b a Department of Genetics, Faculty of Medicine, University of Porto; b Centre for Reproductive Genetics Alberto Barros; and c Lab Cell Biology, ICBAS, University of Porto, Porto, Portugal Objective: To report a novel cystic fibrosis transmembrane conductance regulator (CFTR) gene missense mutation in a compound heterozygote with congenital bilateral absence of the vas deferens (CBAVD). Login to comment 7 ABCC7 p.Pro1290Ser Result(s): The DNA analysis revealed a 7T/7T homozygote at IVS8-T, with a 4000C3T change (P1290S) in exon 20 of the CFTR gene, which was inherited from the patient`s father. Login to comment 9 ABCC7 p.Pro1290Ser Conclusion(s): The novel P1290S missense CFTR mutation causes an amino acid change in a highly conserved region of the CFTR protein that controls channel opening. Login to comment 58 ABCC7 p.Pro1290Ser Analysis of exon 20 in the patient revealed a novel missense mutation, with a C to T nucleotide change at position 4000 (P1290S mutation) that leads to substitution of a proline by a serine in the CFTR protein (Fig. 1A, B). Login to comment 60 ABCC7 p.Pro1290Ser Restriction analysis was thus used to screen and confirm the P1290S mutation as well as reveal that it was inherited from the father and not from the mother (see Fig. 1C). Login to comment 61 ABCC7 p.Pro1290Ser To rule out the possibility of P1290S being a polymorphism, we analyzed 218 normal chromosomes from 109 fertile and healthy Portuguese males, 64 chromosomes from 32 patients with obstructive azoospermia due to congenital absence of the vas deferens (some of them with CFTR mutations identified), 30 chromosomes from 15 children carrying one CFTR mutation, and 10 chromosomes from five patients with confirmed CF (two CFTR mutations detected). Login to comment 62 ABCC7 p.Pro1290Ser In all cases, absence of the P1290S mutation was confirmed as no C3T was found at position 4000 of exon 20 in the CFTR gene. Login to comment 64 ABCC7 p.Pro1290Ser DISCUSSION Direct sequencing and DGGE in a CBAVD heterozygote patient for the 3272-26A3G mutation identified a novel P1290S CFTR mutation. Login to comment 68 ABCC7 p.Pro1290Ser Several lines of evidence suggest that the present P1290S missense CFTR mutation might be pathogenic. Login to comment 71 ABCC7 p.Pro1290Ser ABCC7 p.Pro1290Ser Third, and although the isolated P1290S mutation had no substantial effect per se (the patient`s father is healthy and fertile), when associated with a mild CFTR mutation (P1290S/3272-26A3G) it caused a CBAVD phenotype in the present patient. Login to comment 74 ABCC7 p.Pro1290Ser These data thus support the present findings, where the novel P1290S CFTR mutation was diagnosed at the age of 46 in an infertile CBAVD patient who had no clinical CF phenotype. Login to comment 84 ABCC7 p.Pro1290Ser Novel P1290S CFTR mutation in CBAVD. Login to comment 87 ABCC7 p.Pro1290Ser Novel P1290S CFTR mutation in CBAVD Vol. 83, No. Login to comment