Analysis of pathogenic variants of the mtdna mt- ts1 gene in patients with hearing loss in buryatia

Pathogenic variants of mitochondrial tRNA genes remain poorly understood in the context of the study of the etiology of hearing loss, despite the fact that they are one of the important causes of syndromic and non-syndromic hearing impairment as well as aminoglycoside-induced hearing loss. In this work, we searched for pathogenic variants of the mtDNA MT-TS1 gene in patients with hearing impairments in Buryatia. One rare variant m.7445A>C was found in the MT-TS1 gene out of five investigated variants in one patient (1/165; 0.6%). This variant is localized in the coding region of two genes the MT-CO1 (H-chain) and MT-TS1 (L-chain), but on different mtDNA chains. However, a pathogenetic role for the m.7445A>C substitution has been shown for the MT-TS1 gene, but not for the MT-CO1 gene. In databases, the m.7445A>C variant is associated with nonsyndromic hearing loss, including those caused by aminoglycoside antibiotics. A comparative genotype-phenotypic analysis of our case and four cases with m.7445A>C of the MT-TS1 gene described earlier in the literature showed that hearing loss in all cases is not congenital, but at the same time varies in severity with low penetrance. The results obtained indicate the involvement of other modulating factors in the clinical manifestation of hearing impairment associated with this variant. Thus, further study of rare variants of MT-TS1 gene will contribute to our understanding of the pathogenetic mechanisms of mitochondrial forms of hearing loss.