Identification of four novel connexin 26 mutations in non-syndromic deaf patients: genotype–phenotype analysis in moderate cases
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This paper presents a mutation as well as a genotype–phenotype analysis of the GJB2 and GJB6 genes in 476 samples from non-syndromic unrelated Argentinean deaf patients (104 familial and 372 sporadic cases). Most of them were of prelingual onset (82 %) and 27 % were cochlear implanted. Variation of sequences was detected in 171 of the 474 patients (36 %). Overall, 43 different sequence variations were identified in GJB2 and GJB6. Four of them are reported for the first time in GJB2: c.233dupG, p.Ala78Ser, p.Val190Asp and p.Cys211Tyr. Mutations in GJB6 were detected in 3 % of patients [nine del(GJB6-D13S1830) and three del(GJB6-D13S1854)]. Of the 43 different variations identified in GJB2, 6 were polymorphisms and of the others, 10 (27 %) were truncating and 27 (73 %) were nontruncating. Patients with two truncating mutations had significantly worse hearing impairment than all other groups. Moderate phenotypes were observed in a group of patients carrying biallelic mutations (23 %). This work shows the high prevalence of GJB2 mutations in the Argentinean population and presents an analysis of moderate phenotypes in our cohort.
KeywordsGJB2 Connexin 26 GJB6 Deafness Novel mutations Hearing loss Molecular study Autosomal recessive deafness DFNB1 Moderate hearing loss
We would like to thank all families that participated in this study. This study was supported by an International Research Scholar grant from the Howard Hughes Medical Institute and the Tinnitus Research Initiative to Ana Belen Elgoyhen and by ANPCyT, Argentina, to Viviana Dalamon. María Florencia Wernert is a CONICET fellow.
Conflict of interest
The authors declare no conflicts of interest.
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