TY - JOUR

T1 - Analysis of GJB6 (Сx30) and GJB3 (Сx31) genes in deaf patients with monoallelic mutations in GJB2 (Сx26) gene in the Sakha Republic (Yakutia)

AU - Pshennikova, V. G.

AU - Barashkov, N. A.

AU - Solovyev, A. V.

AU - Romanov, G. P.

AU - Diakonov, E. E.

AU - Sazonov, N. N.

AU - Morozov, I. V.

AU - Bondar, A. A.

AU - Posukh, O. L.

AU - Dzhemileva, L. U.

AU - Khusnutdinova, E. K.

AU - Tomsky, M. I.

AU - Fedorova, S. A.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Тhe DNA testing of autosomal recessive deafness type 1A (DFNB1A, MIM 220290) is complicated when deaf patients have only monoallelic (heterozygous) recessive mutations in the GJB2 (Сх26) gene that is uninformative for establishment of diagnosis. Such patients may be “random” heterozygous carriers of GJB2 mutations as well as have the mutant allele in a cis-regulatory region of GJB2 gene, in element genes encoding other connexins: GJB6 (Сх30) or GJB3 (Сх31). Previous studies of genetic causes of hearing loss in patients from Yakutia were directed to search for only mutations in the GJB2 gene, and the DNA diagnostics was uninformative for 9.7% (38/393) of the patients with monoallelic GJB2 mutations. In this work the search for mutations in genes GJB3 and GJB6 and two deletions с.del(GJB6-D13S1830) and с.del(GJB6-D13S1854) to the cis-regulatory region of GJB2 gene was conducted in 35 patients with GJB2 monoallelic mutations and in 104 normal hearing individuals. The genes studied are two synonymous substitution c.489G>A (р.Leu163Leu) (GJB6) and c.357C>T (р.Asn119Asn) (GJB3) have been found, probably do not have clinical significance, and two nonsynonymous substitution c.301G>A (p.Glu101Lys) (GJB6) and с.580G>A (p.Ala194Thr) (GJB3). Additional experimental evidences are needed for confirmation of pathogenic significance of detected nonsynonymous substitutions in development of hearing loss in studied patients. Diagnosis of the DFNB1A was confirmed in only one patient, who was discovered by the deletion с.del(GJB6-D13S1830) (GJB2) in combination with a recessive mutation с.35delG (GJB2). In general, our results indicate low contribution of mutations in genes GJB6 and GJB3 in hearing loss etiology in Yakutia.

AB - Тhe DNA testing of autosomal recessive deafness type 1A (DFNB1A, MIM 220290) is complicated when deaf patients have only monoallelic (heterozygous) recessive mutations in the GJB2 (Сх26) gene that is uninformative for establishment of diagnosis. Such patients may be “random” heterozygous carriers of GJB2 mutations as well as have the mutant allele in a cis-regulatory region of GJB2 gene, in element genes encoding other connexins: GJB6 (Сх30) or GJB3 (Сх31). Previous studies of genetic causes of hearing loss in patients from Yakutia were directed to search for only mutations in the GJB2 gene, and the DNA diagnostics was uninformative for 9.7% (38/393) of the patients with monoallelic GJB2 mutations. In this work the search for mutations in genes GJB3 and GJB6 and two deletions с.del(GJB6-D13S1830) and с.del(GJB6-D13S1854) to the cis-regulatory region of GJB2 gene was conducted in 35 patients with GJB2 monoallelic mutations and in 104 normal hearing individuals. The genes studied are two synonymous substitution c.489G>A (р.Leu163Leu) (GJB6) and c.357C>T (р.Asn119Asn) (GJB3) have been found, probably do not have clinical significance, and two nonsynonymous substitution c.301G>A (p.Glu101Lys) (GJB6) and с.580G>A (p.Ala194Thr) (GJB3). Additional experimental evidences are needed for confirmation of pathogenic significance of detected nonsynonymous substitutions in development of hearing loss in studied patients. Diagnosis of the DFNB1A was confirmed in only one patient, who was discovered by the deletion с.del(GJB6-D13S1830) (GJB2) in combination with a recessive mutation с.35delG (GJB2). In general, our results indicate low contribution of mutations in genes GJB6 and GJB3 in hearing loss etiology in Yakutia.

KW - autosomal recessive deafness 1A (DFNB1A)

KW - congenital hearing loss

KW - GJB3 (Cx31) gene

KW - GJB6 (Cx30) gene

KW - monoallelic GJB2-mutations

KW - Sakha Republic (Yakutia)

KW - с.del(GJB6-D13S1830)

KW - ALLELE

KW - VARIANTS

KW - CONNEXIN 26 GENE

KW - HEARING IMPAIRMENT

KW - EPITHELIUM

KW - DEL(GJB6-D13S1830)

KW - SERVER

KW - c.del(GJB6-D13S1830)

KW - EXPRESSION

KW - LARGE DELETION

KW - RAT COCHLEA

UR - http://www.scopus.com/inward/record.url?scp=85023627627&partnerID=8YFLogxK

U2 - 10.1134/S1022795417030103

DO - 10.1134/S1022795417030103

M3 - Article

AN - SCOPUS:85023627627

VL - 53

SP - 688

EP - 697

JO - Russian Journal of Genetics

JF - Russian Journal of Genetics

SN - 1022-7954

IS - 6

ER -