title: GJB2 gene mutations causing familial hereditary deafness in Turkey.
abstract: Mutations in Connexin 26 (Cx26) play an important role in autosomal non-syndromic hereditary hearing loss. In this study, our objective was to find out the significance of Cx26 mutations in Turkish families who had hereditary deafness. Fourteen families who had at least two prelingually deaf children per family were included in the study. One affected child from each of the 14 families was selected for single-stranded conformational polymorphism SSCP analysis. Three PCR reactions were used for each subject to amplify the entire Cx26 coding region with overlap. PCR products were sequenced on an Applied Biosystems (ABI) model 3700 automated sequencer. Six of the 14 representative family members (42.9%) demonstrated shifts on SSCP and were subsequently sequenced for Exons 1 and 2 of GJB2 and were tested for the 432 kb upstream deletion. No mutations were found in Exon 1 and no 432 kb deletions were noted. Three different GJB2 mutations were found in Exon 2 of the probands, which were 35delG, 299-300delAT, and 487G > A (M163V). GJB2 mutations were detected in 21.4% of the families. Two patients were homozygous for 35delG and 299-300delAT mutations, and were given a diagnosis of DFNB1 deafness (14.3%). Two different polymorphisms, 457G > A (V153I) and 380G > AG (R127H) were also found. In conclusion, although GJB2 mutations were detected in 21.4% of the families tested, only 14.3% of subject representatives were homozygous and therefore deafness caused by Cx26 mutation segregated with DFNB1. Thus, contribution of GJB2 mutations appears less significant in familial deafness. This necessitates further assessment for the other known gene regions as well as a search for new genetic factors in familial type of genetic deafness.
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, University of Gaziantep, Turkey. bayazity@yahoo.com
authors.forename: Yildirim A
authors.initials: YA
authors.lastname: Bayazit
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Cable
authors.forename: Osman
authors.initials: O
authors.lastname: Cataloluk
authors.forename: Cengiz
authors.initials: C
authors.lastname: Kara
authors.forename: Parker
authors.initials: P
authors.lastname: Chamberlin
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: Muzaffer
authors.initials: M
authors.lastname: Kanlikama
authors.forename: Enver
authors.initials: E
authors.lastname: Ozer
authors.forename: Ecir Ali
authors.initials: EA
authors.lastname: Cakmak
authors.forename: Semih
authors.initials: S
authors.lastname: Mumbuc
authors.forename: Ahmet
authors.initials: A
authors.lastname: Arslan
mesh_terms: D002648:Child; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014421:Turkey
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26