Key result
Novel MYO3A missense variant linked to progressive high-frequency hearing loss.
Why the study?
Only two missense variants in MYO3A had been described in autosomal dominant families with progressive sensorineural hearing loss.
Is a novel missense variant in MYO3A associated with autosomal dominant high-frequency hearing loss?
Observational
Is a novel missense variant in MYO3A associated with autosomal dominant high-frequency hearing loss?
Identifies a novel likely pathogenic variant in MYO3A in a European family, supporting its role as an autosomal dominant hearing loss gene.
Supports expanded MYO3A testing in familial hearing loss; extends variant spectrum but leaves open pathogenicity and prevalence.
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.
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Doll et al. (2020) conducted an observational in Autosomal dominant high-frequency hearing loss. Heterozygous missense variant c.716T>C, p.(Leu239Pro) in MYO3A was evaluated on Hearing level thresholds at high-, mid-, and low-frequencies. A novel heterozygous missense variant c.716T>C, p.(Leu239Pro) in MYO3A was identified as the likely pathogenic cause of autosomal dominant progressive high-frequency hearing loss in a German family.
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