TY - JOUR

T1 - Different Rates of the SLC26A4-Related Hearing Loss in Two Indigenous Peoples of Southern Siberia (Russia)

AU - Danilchenko, Valeriia Yu

AU - Zytsar, Marina V.

AU - Maslova, Ekaterina A.

AU - Bady-Khoo, Marita S.

AU - Barashkov, Nikolay A.

AU - Morozov, Igor V.

AU - Bondar, Alexander A.

AU - Posukh, Olga L.

N1 - Funding Information: Funding: This work was supported by the Ministry of Education and Science of the Russian Federation (grant #2019-0546/FSUS-2020-0040 to O.L.P, V.Y.D., E.A.M., and grant #FSRG-2020-0016 to N.A.B.), by the Budget Projects of the Institute of Cytology and Genetics SB RAS (#AAAA-A19-119100990053-4 to V.Y.D., M.V.Z., and #0259-2021-0014 to O.L.P.), and by the RFBR grants (#17-29-06016_ofi_m and #20-015-00328_A to O.L.P.). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

KW - Altaians

KW - DFNB4

KW - Genetic diagnosis

KW - Hearing loss

KW - Russia

KW - SLC26A4

KW - Southern Siberia

KW - Tuvinians

UR - http://www.scopus.com/inward/record.url?scp=85122212778&partnerID=8YFLogxK

UR - https://www.elibrary.ru/item.asp?id=47550806

U2 - 10.3390/diagnostics11122378

DO - 10.3390/diagnostics11122378

M3 - Article

C2 - 34943614

AN - SCOPUS:85122212778

VL - 11

JO - Diagnostics

JF - Diagnostics

SN - 2075-4418

IS - 12

M1 - 2378

ER -