| Autor: |
Posukh OL; Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia. posukh@bionet.nsc.ru.; Novosibirsk State University, 630090 Novosibirsk, Russia. posukh@bionet.nsc.ru., Zytsar MV; Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia. zytzar@bionet.nsc.ru., Bady-Khoo MS; Research Institute of Medical-Social Problems and Management of the Republic of Tyva, 667000 Kyzyl, Russia. marita.badyhoo@mail.ru.; Perinatal Center of the Republic of Tyva, 667000 Kyzyl, Russia. marita.badyhoo@mail.ru., Danilchenko VY; Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia. danilchenko_valeri@mail.ru., Maslova EA; Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia. maslova@bionet.nsc.ru.; Novosibirsk State University, 630090 Novosibirsk, Russia. maslova@bionet.nsc.ru., Barashkov NA; Yakut Scientific Centre of Complex Medical Problems, 677019 Yakutsk, Russia. barashkov2004@mail.ru.; M.K. Ammosov North-Eastern Federal University, 677027 Yakutsk, Russia. barashkov2004@mail.ru., Bondar AA; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia. alex.bondar@mail.ru., Morozov IV; Novosibirsk State University, 630090 Novosibirsk, Russia. Mor@niboch.nsc.ru.; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia. Mor@niboch.nsc.ru., Maximov VN; Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia. medik11@mail.ru.; Novosibirsk State University, 630090 Novosibirsk, Russia. medik11@mail.ru., Voevoda MI; Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia. voevoda@bionet.nsc.ru.; Novosibirsk State University, 630090 Novosibirsk, Russia. voevoda@bionet.nsc.ru. |
| Abstrakt: |
Mutations in the GJB2 gene are the main cause for nonsyndromic autosomal recessive deafness 1A (DFNB1A) in many populations. GJB2 mutational spectrum and pathogenic contribution are widely varying in different populations. Significant efforts have been made worldwide to define DFNB1A molecular epidemiology, but this issue still remains open for some populations. The main aim of study is to estimate the DFNB1A prevalence and GJB2 mutational spectrum in Tuvinians-an indigenous population of the Tyva Republic (Southern Siberia, Russia). Sanger sequencing was applied to analysis of coding (exon 2) and non-coding regions of GJB2 in a cohort of Tuvinian patients with hearing impairments ( n = 220) and ethnically matched controls ( n = 157). Diagnosis of DFNB1A was established for 22.3% patients (28.8% of familial vs 18.6% of sporadic cases). Our results support that patients with monoallelic GJB2 mutations (8.2%) are coincidental carriers. Recessive mutations p.Trp172Cys, c.-23+1G>A, c.235delC, c.299_300delAT, p.Val37Ile and several benign variants were found in examined patients. A striking finding was a high prevalence of rare variant p.Trp172Cys (c.516G>C) in Tuvinians accounting for 62.9% of all mutant GJB2 alleles and a carrier frequency of 3.8% in controls. All obtained data provide important targeted information for genetic counseling of affected Tuvinian families and enrich current information on variability of GJB2 worldwide. |
