TY - JOUR

T1 - The GJB2 (Cx26) Gene Variants in Patients with Hearing Impairment in the Baikal Lake Region (Russia)

AU - Pshennikova, Vera G

AU - Teryutin, Fedor M

AU - Cherdonova, Alexandra M

AU - Borisova, Tuyara V

AU - Solovyev, Aisen V

AU - Romanov, Georgii P

AU - Morozov, Igor V

AU - Bondar, Alexander A

AU - Posukh, Olga L

AU - Fedorova, Sardana A

AU - Barashkov, Nikolay A

N1 - Funding: This study was supported by the YSC CMP project “Study of the genetic structure and burden of hereditary pathology of the populations of the Republic of Sakha (Yakutia)” (to V.G.P., F.M.T. and N.A.B.), by the Ministry of Science and Higher Education of the Russian Federation (FSRG-2023-0003) (A.M.C., T.V.B., A.V.S., G.P.R. and S.A.F.) and by the Project No FWNR-2022-0021 of the Institute of Cytology and Genetics SB RAS (to O.L.P.).

PY - 2023/4/28

Y1 - 2023/4/28

N2 - The GJB2 (Cx26) gene pathogenic variants are associated with autosomal recessive deafness type 1A (DFNB1A, OMIM #220290). Direct sequencing of the GJB2 gene among 165 hearing-impaired individuals living in the Baikal Lake region of Russia identified 14 allelic variants: pathogenic/likely pathogenic-nine variants, benign-three variants, unclassified-one variant, and one novel variant. The contribution of the GJB2 gene variants to the etiology of hearing impairment (HI) in the total sample of patients was 15.8% (26 out of 165) and significantly differed in patients of different ethnicity (5.1% in Buryat patients and 28.9% in Russian patients). In patients with DFNB1A (n = 26), HIs were congenital/early onset (92.3%), symmetric (88.5%), sensorineural (100.0%), and variable in severity (moderate-11.6%, severe-26.9% or profound-61.5%). The reconstruction of the SNP haplotypes with three frequent GJB2 pathogenic variants (c.-23+1G>A, c.35delG or c.235delC), in comparison with previously published data, supports a major role of the founder effect in the expansion of the c.-23+1G>A and c.35delG variants around the world. Comparative analysis of the haplotypes with c.235delC revealed one major haplotype G A C T (97.5%) in Eastern Asians (Chinese, Japanese and Korean patients) and two haplotypes, G A C T (71.4%) and G A C C (28.6%), in Northern Asians (Altaians, Buryats and Mongols). The variable structure of the c.235delC-haplotypes in Northern Asians requires more studies to expand our knowledge about the origin of this pathogenic variant.

AB - The GJB2 (Cx26) gene pathogenic variants are associated with autosomal recessive deafness type 1A (DFNB1A, OMIM #220290). Direct sequencing of the GJB2 gene among 165 hearing-impaired individuals living in the Baikal Lake region of Russia identified 14 allelic variants: pathogenic/likely pathogenic-nine variants, benign-three variants, unclassified-one variant, and one novel variant. The contribution of the GJB2 gene variants to the etiology of hearing impairment (HI) in the total sample of patients was 15.8% (26 out of 165) and significantly differed in patients of different ethnicity (5.1% in Buryat patients and 28.9% in Russian patients). In patients with DFNB1A (n = 26), HIs were congenital/early onset (92.3%), symmetric (88.5%), sensorineural (100.0%), and variable in severity (moderate-11.6%, severe-26.9% or profound-61.5%). The reconstruction of the SNP haplotypes with three frequent GJB2 pathogenic variants (c.-23+1G>A, c.35delG or c.235delC), in comparison with previously published data, supports a major role of the founder effect in the expansion of the c.-23+1G>A and c.35delG variants around the world. Comparative analysis of the haplotypes with c.235delC revealed one major haplotype G A C T (97.5%) in Eastern Asians (Chinese, Japanese and Korean patients) and two haplotypes, G A C T (71.4%) and G A C C (28.6%), in Northern Asians (Altaians, Buryats and Mongols). The variable structure of the c.235delC-haplotypes in Northern Asians requires more studies to expand our knowledge about the origin of this pathogenic variant.

KW - Humans

KW - Connexins/genetics

KW - Lakes

KW - Mutation

KW - Connexin 26/genetics

KW - Hearing Loss/genetics

KW - Russia

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85160380842&origin=inward&txGid=3289f627199f75ec08f5e60d6306f29a

U2 - 10.3390/genes14051001

DO - 10.3390/genes14051001

M3 - Article

C2 - 37239361

VL - 14

JO - Genes

JF - Genes

SN - 2073-4425

IS - 5

M1 - 1001

ER -