ИЗУЧЕНИЕ НАСЛЕДСТВЕННЫХ ФОРМ ТУГОУХОСТИ / ГЛУХОТЫ В РЕСПУБЛИКЕ ТЫВА. СООБЩЕНИЕ II. ОЦЕНКА СПЕКТРА МУТАЦИЙ В ГЕНЕGJB2 (CX26) И ИХ ВКЛАДА В ЭТИОЛОГИЮ ПОТЕРИ СЛУХА

Marita S Bady-Khoo ,Nikolay A Barashkov ,О С Омзар ,Marina V Zytsar ,Р Ш Монгуш ,Olga V Skidanova ,Alexander A Bondar ,В М Тукар ,И В Морозов ,В Ю Михальская ,Olga L Posukh

doi:10.1234/xxxx-xxxx-2014-11-30-40

Abstract

Here we present the results of the hearing loss genetic component study caused by mutations in the GJB2 (Cx26) gene. The study was conducted in 201 patients from the Republic of Tuva with congenital or early onset severe-profound sensorineural hearing loss. The GJB2 gene recessive mutations p.W172C (c.516G>C), IVS1+1G>A ( с .-23+1G>A), c.235delC, p.V37I (c.109G>A), c.299_300delAT, c.35delG) in homozygous, compound heterozygous or heterozygous mutation states were identified in 70 patients (34.8% of patients), 38 of whom (18.9%) had two GJB2 -mutation, and 32 (15.9%) — only one GJB2 -mutation. Mutational spectrum of the GJB2 gene in studied Tuvinian patients was characterized by the presence of five mutations (p.W172C, IVS1+1G>A, c.235delC, p.V37I, and c.299_300delAT) and GJB2 gene polymorphic variants p.V27I (c.79G>A), p.E114G (c.341A>G), p.V153I (c.457G>A), p.F191L (c.571T>C), p.I203T (c.608T>C), common in the Asian regions while the only mutation c.35delG characteristic for Caucasians has been found in Russian patients. The frequencies of mutations p.W172C, IVS1+1G>A, c.235delC, p.V37I, and c.299_300delAT among all mutant chromosomes in examined Tuvinian patients were 51.49%, 38.61%, 4.95%, 2.97%, and 1.98%, respectively. Total carrier frequency of recessive GJB2 mutations in Tuvinian population sample (n = 121) was 11.57% (p.W172C — 4.96%, IVS1 +1 G>A — 4.13%, p.V37I — 2.48%, respectively). We detected GJB2 mutations in patients that had a history of various environmental etiological factors, presumably leading to their hearing loss. This strongly suggests the necessity for genetic testing in such group of patients as well. Familial cases of «Cx26-negative» hearing loss identified in the Republic of Tuva suggests the presence of other, yet unidentified, genes associated with this pathology. The proportion of patients with hearing loss due to the presence of two recessive GJB2 mutations of the gene is 18.9%, which is a minimal estimation of the genetic component in etiology of hearing loss in the Tuva population.

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