A novel missense variant in MYO3A is associated with autosomal dominant high-frequency hearing loss in a German family
- Mol Genet Genomic Med. 2020 Aug;8(8):e1343. doi: 10.1002/mgg3.1343.
- 1. Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
- 2. Joint Practice of Pediatrics, Regensburg, Germany.
- 3. Institute of Clinical Neurobiology, University Hospital Würzburg, Würzburg, Germany.
- 4. Institute of Bioinformatics, Julius Maximilians University, Würzburg, Germany.
- 5. Tübingen Hearing Research Centre, Department of Otolaryngology - Head and Neck Surgery, Eberhard Karls University, Tübingen, Germany.
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.