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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)

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 epide...

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Autores principales: Posukh, Olga L., Zytsar, Marina V., Bady-Khoo, Marita S., Danilchenko, Valeria Yu., Maslova, Ekaterina A., Barashkov, Nikolay A., Bondar, Alexander A., Morozov, Igor V., Maximov, Vladimir N., Voevoda, Michael I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627114/
https://www.ncbi.nlm.nih.gov/pubmed/31195736
http://dx.doi.org/10.3390/genes10060429
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author Posukh, Olga L.
Zytsar, Marina V.
Bady-Khoo, Marita S.
Danilchenko, Valeria Yu.
Maslova, Ekaterina A.
Barashkov, Nikolay A.
Bondar, Alexander A.
Morozov, Igor V.
Maximov, Vladimir N.
Voevoda, Michael I.
author_facet Posukh, Olga L.
Zytsar, Marina V.
Bady-Khoo, Marita S.
Danilchenko, Valeria Yu.
Maslova, Ekaterina A.
Barashkov, Nikolay A.
Bondar, Alexander A.
Morozov, Igor V.
Maximov, Vladimir N.
Voevoda, Michael I.
author_sort Posukh, Olga L.
collection PubMed
description 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.
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spelling pubmed-66271142019-07-19 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) Posukh, Olga L. Zytsar, Marina V. Bady-Khoo, Marita S. Danilchenko, Valeria Yu. Maslova, Ekaterina A. Barashkov, Nikolay A. Bondar, Alexander A. Morozov, Igor V. Maximov, Vladimir N. Voevoda, Michael I. Genes (Basel) Article 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. MDPI 2019-06-05 /pmc/articles/PMC6627114/ /pubmed/31195736 http://dx.doi.org/10.3390/genes10060429 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Posukh, Olga L.
Zytsar, Marina V.
Bady-Khoo, Marita S.
Danilchenko, Valeria Yu.
Maslova, Ekaterina A.
Barashkov, Nikolay A.
Bondar, Alexander A.
Morozov, Igor V.
Maximov, Vladimir N.
Voevoda, Michael 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)
title 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)
title_full 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)
title_fullStr 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)
title_full_unstemmed 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)
title_short 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)
title_sort 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)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627114/
https://www.ncbi.nlm.nih.gov/pubmed/31195736
http://dx.doi.org/10.3390/genes10060429
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