TY - JOUR

T1 - Insight into the Natural History of Pathogenic Variant c.919-2A>G in the SLC26A4 Gene Involved in Hearing Loss: The Evidence for Its Common Origin in Southern Siberia (Russia)

AU - Danilchenko, Valeriia Yu

AU - Zytsar, Marina V

AU - Maslova, Ekaterina A

AU - Orishchenko, Konstantin E

AU - Posukh, Olga L

N1 - Funding: This work was supported by the Russian Science Foundation (grant No. 21-75-00030, https://rscf.ru/en/project/21-75-00030/, to M.V.Z. and E.A.M.); by the projects of the Institute of Cytology and Genetics SB RAS (No. FWNR-2022-0003 to V.Y.D. and No. FWNR-2022-0021 to O.L.P.); and by the Ministry of Education and Science of Russian Federation (grant No. FSUS-2020-0040 to O.L.P. and K.E.O.).

PY - 2023/4/17

Y1 - 2023/4/17

N2 - Pathogenic variants in the SLC26A4 gene leading to nonsyndromic recessive deafness (DFNB4), or Pendred syndrome, are some of the most common causes of hearing loss worldwide. Earlier, we found a high proportion of SLC26A4-related hearing loss with prevailing pathogenic variant c.919-2A>G (69.3% among all mutated SLC26A4 alleles that have been identified) in Tuvinian patients belonging to the indigenous Turkic-speaking Siberian people living in the Tyva Republic (Southern Siberia, Russia), which implies a founder effect in the accumulation of c.919-2A>G in Tuvinians. To evaluate a possible common origin of c.919-2A>G, we genotyped polymorphic STR and SNP markers, intragenic and flanking SLC26A4, in patients homozygous for c.919-2A>G and in healthy controls. The common STR and SNP haplotypes carrying c.919-2A>G were revealed, which convincingly indicates the origin of c.919-2A>G from a single ancestor, supporting a crucial role of the founder effect in the c.919-2A>G prevalence in Tuvinians. Comparison analysis with previously published data revealed the identity of the small SNP haplotype (~4.5 kb) in Tuvinian and Han Chinese carriers of c.919-2A>G, which suggests their common origin from founder chromosomes. We assume that c.919-2A>G could have originated in the geographically close territories of China or Tuva and subsequently spread to other regions of Asia. In addition, the time intervals of the c.919-2A>G occurrence in Tuvinians were roughly estimated.

AB - Pathogenic variants in the SLC26A4 gene leading to nonsyndromic recessive deafness (DFNB4), or Pendred syndrome, are some of the most common causes of hearing loss worldwide. Earlier, we found a high proportion of SLC26A4-related hearing loss with prevailing pathogenic variant c.919-2A>G (69.3% among all mutated SLC26A4 alleles that have been identified) in Tuvinian patients belonging to the indigenous Turkic-speaking Siberian people living in the Tyva Republic (Southern Siberia, Russia), which implies a founder effect in the accumulation of c.919-2A>G in Tuvinians. To evaluate a possible common origin of c.919-2A>G, we genotyped polymorphic STR and SNP markers, intragenic and flanking SLC26A4, in patients homozygous for c.919-2A>G and in healthy controls. The common STR and SNP haplotypes carrying c.919-2A>G were revealed, which convincingly indicates the origin of c.919-2A>G from a single ancestor, supporting a crucial role of the founder effect in the c.919-2A>G prevalence in Tuvinians. Comparison analysis with previously published data revealed the identity of the small SNP haplotype (~4.5 kb) in Tuvinian and Han Chinese carriers of c.919-2A>G, which suggests their common origin from founder chromosomes. We assume that c.919-2A>G could have originated in the geographically close territories of China or Tuva and subsequently spread to other regions of Asia. In addition, the time intervals of the c.919-2A>G occurrence in Tuvinians were roughly estimated.

KW - Humans

KW - Siberia/epidemiology

KW - Mutation

KW - Hearing Loss/genetics

KW - Deafness/genetics

KW - Russia

KW - Sulfate Transporters/genetics

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85153958876&origin=inward&txGid=1c15b39dc6e7b45c5ab56e8a4c3ec453

U2 - 10.3390/genes14040928

DO - 10.3390/genes14040928

M3 - Article

C2 - 37107686

VL - 14

JO - Genes

JF - Genes

SN - 2073-4425

IS - 4

M1 - 928

ER -