Molecular diagnostics of hearing loss due to mutations in the SLC26A4 gene in indigenous peoples of Southern Siberia (Russia)

Poster (download) Valeriia Yuryevna Danilchenko1, Marina Vyacheslavovna Zytsar2, Marita Sergeevna Bady-Khoo3, Ekaterina Alexandrovna Maslova4, Olga Leonidovna Posukh51Federal Research Center Institute of Cytology and Genetics, danilchenko_valeri@mail.ru2Federal Research Center Institute of Cytology and Genetics, zytzar@bionet.nsc.ru3Perinatal Center of the Republic of Tyva, marita.badyhoo@mail.ru4Federal Research Center Institute of Cytology and Genetics; Novosibirsk State University, maslova@bionet.nsc.ru5Federal Research Center Institute of Cytology and Genetics; Novosibirsk State University, posukh@bionet.nsc.ru Establishing a genetic diagnosis of hearing loss is of great importance for clinical evaluation of deaf patients and for estimating recurrence risks for their families. Mutations in the SLC26A4 gene are a common cause of hearing loss in many regions of the world. This study presents the results of the first molecular genetic analysis of the SLC26A4 gene sequence performed in patients with hearing loss of unknown etiology belonging to indigenous peoples of Southern Siberia – Tuvinians (the Tyva Republic) and Altaians (the Altai Republic). Contrast differences of the SLC26A4 pathogenic contribution to the etiology of hearing impairment were revealed: 28.2% for Tuvinians and 4.3% for Altaians. Both known and novel pathogenic variants as well as a wide range of polymorphic variants were found in the SLC26A4 gene sequences of examined patients. High frequency of mutation c.919-2A>G in Tuvinians is probably due to the founder effect.

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Generation of the panel of transgenic human cell lines with stable expression of mutant variants of the GJB2 gene associated with hearing loss for comparative in vitro studies

Poster (download) Ekaterina Alexandrovna Maslova1, Marina Vyacheslavovna Zytsar2, Valeriia Yuryevna Danilchenko3, Olga Leonidovna Posukh4, Konstantin Evgenyevich Orishchenko51Federal Research Center Institute of Cytology and Genetics, Novosibirsk State University, Novosibirsk, Russian Federation, maslova@bionet.nsc.ru2Federal Research Center Institute of Cytology and Genetics, Novosibirsk, Russian Federation, zytzar@bionet.nsc.ru3Federal Research Center Institute of Cytology and Genetics, Novosibirsk, Russian Federation, danilchenko_valeri@mail.ru4Federal Research Center Institute of Cytology and Genetics, Novosibirsk State University, Novosibirsk, Russian Federation, posukh@bionet.nsc.ru5Federal Research Center Institute of Cytology and Genetics, Novosibirsk State University, Novosibirsk, Russian Federation, OrishchenkoKE@icg.sbras.ru Assessment of pathogenicity of novel variants is a primary task for molecular diagnostics of hereditary diseases, and comprehensive evidences, including functional in vitro studies, are necessary to support their involving in pathology. Mutations in the GJB2 gene encoding transmembrane protein Cx26 are the common cause for hearing loss worldwide. About 400 pathogenic and also not yet classified variants with ambiguous functional significance are described in the GJB2 gene sequence. In this study, for the first time, the panel of transgenic HeLa cell lines stably expressing of different GJB2 variants was generated for subsequent comparative analysis of structure and functioning of the Cx26 protein. This panel was successfully applied for confirmation of the pathogenicity of novel GJB2 missense variant c.516G>C (p.Trp172Cys) found with high frequency in deaf patients from Southern Siberia.

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