Analysis of the Spectrum of the mtDNA Haplogroups in Patients with Hearing Loss Carrying the Likely Pathogenic Ultra-Rare m.1494C>T Variant in the Gene

The contribution of the m.1494C>T variant of the gene associated with aminoglycoside-induced deafness (, OMIM 561000) to the etiology of hearing loss (HL) is still poorly studied. In this regard, aim of the study – screening of the m.1494C>T gene among patients with HL in the Republic of Buryatia located in the Baikal Lake region of Russia and reconstructed the mitochondrial lineages in 27 patients with m.1494C>T variant from different regions of the world. From available data and based on the results of a genome-wide analysis of mtDNA of one patient with m.1494C>T detected in this study we are reconstructed the mitochondrial lineages in 27 patients with m.1494C>T variant from different regions of the world. As a result, 19 different mtDNA haplogroups were identified, which likely indicates the independent origin of the m.1494C>T variant on the different mitochondrial background. However, in patients with m.1494C>T were found the high frequency of haplogroup A* (18.5%, 5/27), which in 13 times exceeded (χ = 45.274; p < 0.001) the mean frequency of this haplogroup (1.45%, 519/35748) in worldwide population. The over representation of haplogroup A* among patients with m.1494C>T may be due of their common ancestry. The possible influence of a founder effect on the prevalence of the , the target screening of the m.1494C>T variant in previously unexplored cohorts of patients with HL is a more relevant, primarily in regions where the haplogroups A* and A2 were found – in Asia and America.