The p.R206C Mutation in MYO7A Leads to Autosomal Dominant Nonsyndromic Hearing Loss

Background:Dominant mutations inMYO7Amay lead to nonsyndromic deafness DFNA11. A p.R206C variant inMYO7Ahas previously been reported in a small deaf family from Taiwan but with ambiguous pathogenicity and inheritance pattern.Aims/Objectives: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.Materials and Methods: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.Results: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 inMYO7Aas the only candidate pathogenic mutation cosegregating with the hearing phenotype. This mutation is not seen in 200 Chinese Han normal-hearing controls.Conclusions and Significance:The recurrent p.R206C variant inMYO7Ais 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.