ABCMdb

PMID: 7477025

Tzetis M, Kanavakis E, Antoniadi T, Traeger-Synodinos J, Doudounakis S, Adam G, Kattamis C
Identification of two novel mutations (296 + 1G-C and A46D) in exon 2 of the CFTR gene in Greek cystic fibrosis patients.
Mol Cell Probes. 1995 Aug;9(4):283-5., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Ala46Asp MolecularandCellularProbes(1995) 9, 283-285 Short Communication Identification of two novel mutations (296+ 1G-C and A46D) in exon 2 of the CFTR gene in Greek cystic fibrosis patients Maria Tzetis, ~ Emmanuel Kanavakis, ~ Thalia Antoniadi, 1 Joanne Traeger- Synodinos, 1 Stavros Doudounakis, 2 George Adam 2 and Christos Kattamis t* 1First Department of Pediatrics, Athens University, and 2Cystic Fibrosis Clinic, St. Sophia's Children's Hospital, Athens 11527, Greece (Received 30 March, Accepted 6 April) Two novel CFTR mutations were detected in Greek cystic fibrosis patients. Login to comment 1 ABCC7 p.Ala46Asp One was a missense mutation, A46D, and the other a splice mutation, 296+ 1G-C. Login to comment 4 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Since the identification of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein and the initial characterization of the predominant mutation in the Caucasian population, AF508,'-~ more than 400 other mutations have been reported.4 Mutations have been described in all of the exons and neighbouring intronic sequences of the CFTR gene, with highest concentration of the more common mutations occuring in exons coding for NBF1.s To determine the type and frequency of cystic fibrosis (CF) mutations in the Greek population we screened 184 patientsfor the most common mutations (,4F508, G542X, G551D, 621 +IG>T, N1303K and W1282X) by ASO hybridization and then proceeded to analyseexons2, 4, 5, 6a, 6b, 7, 8, 9, 10, 11,17b, 19, 20, and 21 by denaturing gradient gel electrophoresis (DGGE) asdescribed.6The DNA sequence of samples showing a shift in mobility was determined after as- symetric PCR as describedZ The six most common mutations accounted for 66-9% of the CF alleles in Greek patients, of which /IF508 had a frequency of 52.7%. Login to comment 6 ABCC7 p.Ala46Asp Thisapproach allowed mutationsto be identified in 75-3% of all CFalleles in our population.8 While screening our panel of Greek CF chromosomes for mutations in exon 2, we identified two novel mutations of the CFTR gene; one a missense mutation, named A46D, and the other an mRNA splicing mutation, 296 + 1G-C. Login to comment 7 ABCC7 p.Ala46Asp A46D This novel missence mutation was found in samples of two unrelated CF patients of Greek origin (0.5% of all CF alleles). Login to comment 8 ABCC7 p.Gly542* ABCC7 p.Ala46Asp One was a compound heterozygote A46D/G542X and the other a compound heterozygote with the 621 +IG-T mutation. Login to comment 9 ABCC7 p.Ala46Asp Sequencing data from the CF patients and their A46D carrier parent's DNA samples revealed a C-A substitution * Authorto whomcorrespondenceshouldbeaddressedat: FirstDepartmentof Pediatrics,AthensUniversity,St.Sophia'sChildren's Hospital,Athens11527, Greece. Login to comment 12 ABCC7 p.Gly542* ABCC7 p.Ala46Asp ABCC7 p.Ala46Asp 1 2 3 CFTR genotype A46D/G542X A46D/621 +IG-T 296+1G-C/ unknown Sex Female Female Male Date of birth 1983 1965 1967 Age at diagnosis 4 years 4.5 years 26 years Sweat test chloride conc. Login to comment 20 ABCC7 p.Ala46Asp We cannot conclude anything about the severity of the A46D mutation, since one of our patients is PI and the other PS, although missense mutations located in the first transmembrane domain are usually associated with mild clinical severity and with pancreatic sufficiency. Login to comment 25 ABCC7 p.Ala46Asp DNA sequence analysis of the novel missense mutation A46D, which is a C-A transversion at nucleotide position 269 of the coding region of exon 2. Login to comment 26 ABCC7 p.Ala46Asp DNA sequence analysis of the novel missense mutation A46D, which is a C-A transversion at nucleotide position 269 of the coding region of exon 2. Login to comment