Rare Missense Variants in MYO7A and OTOP2 Genes in a South Korean Meniere Disease Cohort
Pham, M. T.; Cruz-Granados, P.; Jang, S. H.; Gee, H. Y.; Jung, J.; Choi, J. Y.; Kim, S. H.; Lopez-Escamez, J. A.
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Meniere disease (MD) is a polygenic condition defined by episodes of vertigo associated with sensorineural hearing loss and tinnitus. Genetic studies in familial MD in East Asian population are limited and the potential MD genes remain to be established in non-Finnish European populations. By exome sequencing and rare variant analysis, we search for existing and novel genes associated with MD in a South Korean cohort of 16 MD individuals with bilateral sensorineural hearing loss. We have found one individual with two rare missense variants in the OTOP2 gene, a new candidate gene for MD and three heterozygous variants in the MYO7A gene, supporting the hypothesis of biallelic inheritance. Protein modelling was conducted on three rare missense variants in OTOP2 to further elucidate functional consequences. The structural and functional implications inferred from these models suggest a likely pathogenic role, providing additional insights into the molecular mechanisms underlying MD.