The p.R206C Mutation in <b><i>MYO7A</i></b> Leads to Autosomal Dominant Nonsyndromic Hearing Loss

<b><i>Background:</i></b> Dominant mutations in <i>MYO7A</i> may lead to nonsyndromic deafness DFNA11. A p.R206C variant in <i>MYO7A</i> has previously been reported in a small deaf family from Taiwan but with ambiguous pathogenicity and inheritance pattern. <b><i>Aims/Objectives:</i></b> Our study aims to clarify the pathogenicity of this variant by clinical characterization and genetic analysis of a separate autosomal dominant deaf family harboring this variant in mainland China. <b><i>Materials and Methods:</i></b> Auditory features of hearing loss were characterized in representative affected family members. Mutation screening was performed by targeted next-generation sequencing of 138 known deafness genes in the proband. Candidate pathogenic mutations were confirmed by Sanger sequencing in family members and ethnically matched controls. <b><i>Results:</i></b> Consistent with typical DFNA11 phenotype, the affected family members in this study showed delayed-onset, progressive hearing loss affecting mostly high frequencies. Targeted next-generation sequencing identified a p.R206C mutation in <i>MYO7A</i> as the only candidate pathogenic mutation cosegregating with the hearing phenotype. This mutation is not seen in 200 Chinese Han normal-hearing controls. <b><i>Conclusions and Significance:</i></b> The recurrent p.R206C variant in <i>MYO7A</i> is pathogenic and is likely in a mutation hot spot or due to a founder effect. Reports of such rare variants in multiple patients or families may facilitate exploitation of its pathogenicity.