Enviar artigo por via de e-mail Analysis of GJB6 (Сx30) and GJB3 (Сx31) genes in deaf patients with monoallelic mutations in GJB2 (Сx26) gene in the Sakha Republic (Yakutia)
- Autores: Pshennikova V.G.1,2, Barashkov N.A.1,2, Solovyev A.V.1,2, Romanov G.P.1,2, Diakonov E.E.2, Sazonov N.N.2, Morozov I.V.3,4, Bondar A.A.3, Posukh O.L.5,4, Dzhemileva L.U.6, Khusnutdinova E.K.6,7, Tomsky M.I.1, Fedorova S.A.1,2
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Afiliações:
- Yakut Scientific Center of Сomplex Мedical Рroblems
- Ammosov Institute of Natural Sciences
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch
- National Research University Novosibirsk State University
- Institute of Cytology and Genetics, Siberian Branch
- Institute of Biochemistry and Genetics, Ufa Scientific Centre
- Department of Genetics and Fundamental Medicine
- Edição: Volume 53, Nº 6 (2017)
- Páginas: 688-697
- Seção: Human Genetics
- URL: https://journals.rcsi.science/1022-7954/article/view/188303
- DOI: https://doi.org/10.1134/S1022795417030103
- ID: 188303
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Resumo
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.
Sobre autores
V. Pshennikova
Yakut Scientific Center of Сomplex Мedical Рroblems; Ammosov Institute of Natural Sciences
Autor responsável pela correspondência
Email: psennikovavera@mail.ru
Rússia, Yakutsk, 677010; Yakutsk, 677010
N. Barashkov
Yakut Scientific Center of Сomplex Мedical Рroblems; Ammosov Institute of Natural Sciences
Email: psennikovavera@mail.ru
Rússia, Yakutsk, 677010; Yakutsk, 677010
A. Solovyev
Yakut Scientific Center of Сomplex Мedical Рroblems; Ammosov Institute of Natural Sciences
Email: psennikovavera@mail.ru
Rússia, Yakutsk, 677010; Yakutsk, 677010
G. Romanov
Yakut Scientific Center of Сomplex Мedical Рroblems; Ammosov Institute of Natural Sciences
Email: psennikovavera@mail.ru
Rússia, Yakutsk, 677010; Yakutsk, 677010
E. Diakonov
Ammosov Institute of Natural Sciences
Email: psennikovavera@mail.ru
Rússia, Yakutsk, 677010
N. Sazonov
Ammosov Institute of Natural Sciences
Email: psennikovavera@mail.ru
Rússia, Yakutsk, 677010
I. Morozov
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch; National Research University Novosibirsk State University
Email: psennikovavera@mail.ru
Rússia, Novosibirsk, 630090; Novosibirsk, 630090
A. Bondar
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch
Email: psennikovavera@mail.ru
Rússia, Novosibirsk, 630090
O. Posukh
Institute of Cytology and Genetics, Siberian Branch; National Research University Novosibirsk State University
Email: psennikovavera@mail.ru
Rússia, Novosibirsk, 630090; Novosibirsk, 630090
L. Dzhemileva
Institute of Biochemistry and Genetics, Ufa Scientific Centre
Email: psennikovavera@mail.ru
Rússia, Ufa, 450054
E. Khusnutdinova
Institute of Biochemistry and Genetics, Ufa Scientific Centre; Department of Genetics and Fundamental Medicine
Email: psennikovavera@mail.ru
Rússia, Ufa, 450054; Ufa, 450076
M. Tomsky
Yakut Scientific Center of Сomplex Мedical Рroblems
Email: psennikovavera@mail.ru
Rússia, Yakutsk, 677010
S. Fedorova
Yakut Scientific Center of Сomplex Мedical Рroblems; Ammosov Institute of Natural Sciences
Email: psennikovavera@mail.ru
Rússia, Yakutsk, 677010; Yakutsk, 677010
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