Different Rates of the SLC26A4-Related Hearing Loss in Two Indigenous Peoples of Southern Siberia (Russia).

Valeriia Yu Danilchenko,Nikolay A Barashkov,Ekaterina A Maslova,Marita S Bady-Khoo,Alexander A Bondar,Marina V Zytsar,Olga L Posukh,Igor V Morozov

doi:10.3390/diagnostics11122378

Abstract

Hereditary hearing loss (HL) is known to be highly locus/allelic heterogeneous, and the prevalence of different HL forms significantly varies among populations worldwide. Investigation of region-specific landscapes of hereditary HL is important for local healthcare and medical genetic services. Mutations in the SLC26A4 gene leading to nonsyndromic recessive deafness (DFNB4) and Pendred syndrome are common genetic causes of hereditary HL, at least in some Asian populations. We present for the first time the results of a thorough analysis of the SLC26A4 gene by Sanger sequencing in the large cohorts of patients with HL of unknown etiology belonging to two neighboring indigenous Turkic-speaking Siberian peoples (Tuvinians and Altaians). A definite genetic diagnosis based on the presence of biallelic SLC26A4 mutations was established for 28.2% (62/220) of all enrolled Tuvinian patients vs. 4.3% (4/93) of Altaian patients. The rate of the SLC26A4-related HL in Tuvinian patients appeared to be one of the highest among populations worldwide. The SLC26A4 mutational spectrum was characterized by the presence of Asian-specific mutations c.919-2A>G and c.2027T>A (p.Leu676Gln), predominantly found in Tuvinian patients, and c.2168A>G (p.His723Arg), which was only detected in Altaian patients. In addition, a novel pathogenic variant c.1545T>G (p.Phe515Leu) was found with high frequency in Tuvinian patients. Overall, based on the findings of this study and our previous research, we were able to uncover the genetic causes of HL in 50.5% of Tuvinian patients and 34.5% of Altaian patients.

Highlights

Hearing loss (HL) is one of the most common sensory disorders affecting over 5% of the world’s population [1]
111 single/sporadic HL cases while the group of Altaian patients included 36 familial and 26 single/sporadic HL cases. These patients were selected from the main groups of Tuvinian (n = 220) and Altaian (n = 93) patients and represent individuals in whom the causes of HL remained unknown after the thorough testing for the GJB2 gene [45,48,49,51] and the target screening of several mutations in other genes (MT-RNR1, MT-TS1, OTOF, RAI1) [46,47,50]
Analysis of the SLC26A4 gene was performed in ethnically matched cohorts of patients

Summary

Introduction

Hearing loss (HL) is one of the most common sensory disorders affecting over 5% of the world’s population [1]. Half of all HL cases are attributed to genetic causes [2]. Hereditary HL includes many different syndromes with HL as one of the clinical symptoms and more common nonsyndromic forms. Over 160 nuclear genes are causally implicated in nonsyndromic HL with different types of inheritance: autosomal dominant—. Mutations in the GJB2 gene (13q12.11, OMIM 121011) encoding transmembrane protein connexin 26 result in the nonsyndromic autosomal recessive deafness 1A (DFNB1A, OMIM 220290), which is one of the most common forms of HL in many populations, at least of Caucasian descent [5]. Testing of GJB2 mutations is efficient for establishing a genetic diagnosis in many HL cases. The causes of HL in a large number of patients often remain unknown because of high locus/allelic heterogeneity and varying prevalence of hereditary HL in different populations

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