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Open AccessArticle

Unique Mutational Spectrum of the GJB2 Gene and Its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys)

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Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
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Novosibirsk State University, 630090 Novosibirsk, Russia
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Research Institute of Medical-Social Problems and Management of the Republic of Tyva, 667000 Kyzyl, Russia
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Perinatal Center of the Republic of Tyva, 667000 Kyzyl, Russia
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Yakut Scientific Centre of Complex Medical Problems, 677019 Yakutsk, Russia
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M.K. Ammosov North-Eastern Federal University, 677027 Yakutsk, Russia
7
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
*
Author to whom correspondence should be addressed.
Genes 2019, 10(6), 429; https://doi.org/10.3390/genes10060429
Received: 8 May 2019 / Revised: 30 May 2019 / Accepted: 3 June 2019 / Published: 5 June 2019
(This article belongs to the Special Issue Genetic Epidemiology of Deafness)
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. View Full-Text
Keywords: hearing loss; nonsyndromic autosomal recessive deafness 1A (DFNB1A); GJB2; Tuvinians; Southern Siberia; Russia hearing loss; nonsyndromic autosomal recessive deafness 1A (DFNB1A); GJB2; Tuvinians; Southern Siberia; Russia
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Posukh, O.L.; Zytsar, M.V.; Bady-Khoo, M.S.; Danilchenko, V.Y.; Maslova, E.A.; Barashkov, N.A.; Bondar, A.A.; Morozov, I.V.; Maximov, V.N.; Voevoda, M.I. Unique Mutational Spectrum of the GJB2 Gene and Its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys). Genes 2019, 10, 429.

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