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

Background: Dominant mutations in MYO7A may lead to nonsyndromic deafness DFNA11. A p.R206C variant in MYO7A has 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 in MYO7A as 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 in MYO7A 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.