A novel missense variant in MYO3A is associated with autosomal dominant high‐frequency hearing loss in a German family

BACKGROUND: MYO3A, encoding the myosin IIIA protein, is associated with autosomal recessive and autosomal dominant nonsyndromic hearing loss. To date, only two missense variants located in the motor‐head domain of MYO3A have been described in autosomal dominant families with progressive, mild‐to‐profound sensorineural hearing loss. These variants alter the ATPase activity of myosin IIIA. METHODS: Exome sequencing of a proband from a three‐generation German family with prelingual, moderate‐to‐profound, high‐frequency hearing loss was performed. Segregation analysis confirmed a dominant inheritance pattern. Regression analysis of mean hearing level thresholds per individual and ear was performed at high‐, mid‐, and low‐frequencies. RESULTS: A novel heterozygous missense variant c.716T>C, p.(Leu239Pro) in the kinase domain of MYO3A was identified that is predicted in silico as disease causing. High‐frequency, progressive hearing loss was identified. CONCLUSION: Correlation analysis of pure‐tone hearing thresholds revealed progressive hearing loss, especially in the high‐frequencies. In the present study, we report the first dominant likely pathogenic variant in MYO3A in a European family and further support MYO3A as an autosomal dominant hearing loss gene.