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)

Valeriia Yu Danilchenko; Marina V Zytsar; Ekaterina A Maslova; Konstantin E Orishchenko; Olga L Posukh

doi:10.3390/genes14040928

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)

Genes (Basel). 2023 Apr 17;14(4):928. doi: 10.3390/genes14040928.

Authors

Valeriia Yu Danilchenko^{1

2}, Marina V Zytsar¹, Ekaterina A Maslova^{1

2}, Konstantin E Orishchenko^{1

2}, Olga L Posukh^{1

2}

Affiliations

¹ Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
² Novosibirsk State University, 630090 Novosibirsk, Russia.

Abstract

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.

Keywords: SLC26A4; STR and SNP haplotypes; Tuvinians; c.919-2A>G; founder effect; hearing loss.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Deafness* / genetics
Hearing Loss* / genetics
Humans
Mutation
Russia
Siberia / epidemiology
Sulfate Transporters / genetics

Substances

SLC26A4 protein, human
Sulfate Transporters

Supplementary concepts

Nonsyndromic Deafness

Grants and 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.).