TY - JOUR

T1 - Unique mutational spectrum of the GJB2 gene and its pathogenic contribution to deafness in tuvinians (Southern siberia, russia)

T2 - A high prevalence of rare variant c.516G>C (p.trp172Cys)

AU - Posukh, Olga L.

AU - Zytsar, Marina V.

AU - Bady-Khoo, Marita S.

AU - Danilchenko, Valeria Yu

AU - Maslova, Ekaterina A.

AU - Barashkov, Nikolay A.

AU - Bondar, Alexander A.

AU - Morozov, Igor V.

AU - Maximov, Vladimir N.

AU - Voevoda, Michael I.

PY - 2019/6/5

Y1 - 2019/6/5

N2 - 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.

AB - 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.

KW - GJB2

KW - Hearing loss

KW - Nonsyndromic autosomal recessive deafness 1A (DFNB1A)

KW - Russia

KW - Southern Siberia

KW - Tuvinians

KW - POPULATION

KW - nonsyndromic autosomal recessive deafness 1A (DFNB1A)

KW - CONNEXIN-30 GENE

KW - GENOTYPE

KW - AMINO-ACID SUBSTITUTIONS

KW - SENSORINEURAL HEARING IMPAIRMENT

KW - DELETION

KW - REGION

KW - CONSEQUENCES

KW - HIGH-FREQUENCY

KW - hearing loss

KW - PROMOTER

UR - http://www.scopus.com/inward/record.url?scp=85068859824&partnerID=8YFLogxK

U2 - 10.3390/genes10060429

DO - 10.3390/genes10060429

M3 - Article

C2 - 31195736

AN - SCOPUS:85068859824

VL - 10

JO - Genes

JF - Genes

SN - 2073-4425

IS - 6

M1 - 429

ER -