The m.1555A>G variant of the MT-RNR1 gene of mitochondrial DNA is the main cause of hearing loss in the Republic of Buryatia

Mitochondrial forms of hearing loss account for no more than 1-2% among all non-syndromic cases of hearing loss. However, one of the most common causative variants of the mitochondrial genome is m.1555A>G of the MT-RNR1 gene, which is associated with a deafness induced by aminoglycoside antibiotics (OMIM:561000). Currently, the contribution of the mitochondrial deafness to the etiology of hearing loss remains insufficiently studied, since the detection of the m.1555A>G of the MT-RNR1 gene is not included in all research protocols. In this work, using PCR-RFLP analysis followed by Sanger sequencing, the pathogenic variant m.1555A>G of the MT-RNR1 gene for the first time was searched in 165 hearing impaired patients in the Republic of Buryatia. As a result, the m.1555A>G of the MT-RNR1 gene in the homoplasmic state was detected in 21 out of 165 studied patients. The total contribution of the m.1555A>G (MT-RNR1 gene) to the etiology of hearing impairment in Buryatia was 12.7%. At the same time, a high proportion of m.1555A>G of the MT-RNR1 gene was detected in Buryat patients (20.2%), compared to Russian patients (1.3%). A genetic-epidemiological analysis of the identified mitochondrial form of hearing loss revealed its increased prevalence in three south districts in the Republic of Buryatia, with the maximum accumulation in the Dzhidinskii district (4.5 per 10,000 peoples). The analysis of the global prevalence of the variant m.1555A>G of the MT-RNR1 gene among 43435 patients with hearing impairment showed that its share is on average 1.9%. The results obtained on the high contribution of the m.1555A>G to the etiology of hearing impairment in Buryat patients indicate that we have found in the Baikal Lake region one of the largest of the world accumulation of the mitochondrial forms of hearing loss with most likely due to founder effect.

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