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

  • Human Genetics
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Abstract

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.

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Authors and Affiliations

  1. Yakut Scientific Center of Сomplex Мedical Рroblems, Yakutsk, 677010, Russia

    V. G. Pshennikova, N. A. Barashkov, A. V. Solovyev, G. P. Romanov, M. I. Tomsky & S. A. Fedorova

  2. Ammosov Institute of Natural Sciences, North-Eastern Federal University, Yakutsk, 677010, Russia

    V. G. Pshennikova, N. A. Barashkov, A. V. Solovyev, G. P. Romanov, E. E. Diakonov, N. N. Sazonov & S. A. Fedorova

  3. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Genomics Core Facility, Novosibirsk, 630090, Russia

    I. V. Morozov & A. A. Bondar

  4. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    O. L. Posukh

  5. National Research University Novosibirsk State University, Novosibirsk, 630090, Russia

    I. V. Morozov & O. L. Posukh

  6. Institute of Biochemistry and Genetics, Ufa Scientific Centre, Russian Academy of Sciences, Ufa, 450054, Russia

    L. U. Dzhemileva & E. K. Khusnutdinova

  7. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, 450076, Russia

    E. K. Khusnutdinova

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  1. V. G. Pshennikova
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  2. N. A. Barashkov
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  7. I. V. Morozov
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  9. O. L. Posukh
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Correspondence to V. G. Pshennikova.

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Original Russian Text © V.G. Pshennikova, N.A. Barashkov, A.V. Solovyev, G.P. Romanov, E.E. Diakonov, N.N. Sazonov, I.V. Morozov, A.A. Bondar, O.L. Posukh, L.U. Dzhemileva, E.K. Khusnutdinova, M.I. Tomsky, S.A. Fedorova, 2017, published in Genetika, 2017, Vol. 53, No. 6, pp. 705–715.

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Pshennikova, V.G., Barashkov, N.A., Solovyev, A.V. et al. Analysis of GJB6 (Сx30) and GJB3 (Сx31) genes in deaf patients with monoallelic mutations in GJB2 (Сx26) gene in the Sakha Republic (Yakutia). Russ J Genet 53, 688–697 (2017). https://doi.org/10.1134/S1022795417030103

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