A novel MYO6 variant identified in a Chinese family with autosomal dominant non-syndromic hearing loss.

BACKGROUND: Hereditary hearing loss (HL) is a highly heterogeneous disorder that follows various inheritance patterns. Variants of MYO6 gene in DFNA22 are characterised by progressive post-lingual sensorineural HL of varying severity. PATIENTS AND METHODS: Five-generation Chinese family with autosomal dominant non-syndromic hearing loss (ADNSHL) was enrolled in this study. Whole-exome sequencing (WES) was performed on the proband and her father to screen for causal variants in the genome, whereas intrafamilial co-segregation of the candidate variants in family members was verified using Sanger sequencing. Furthermore, protein modelling and stability analyses were performed to assess the potential pathogenicity of the candidate mutations. RESULTS: A previously unreported heterozygous missense variant (NM_004999.4:c.2063 A > G, p.Gln688Arg) in exon 20 of MYO6 using WES and was found to co-segregated with the disease in this family. Molecular dynamics simulations predict that the glutamic acid-to-arginine change in p.(Gln688Arg) alters the normal function, most likely through the altered intermolecular forces of this amino acid with the three nearby polar residues. The structural changes caused by this mutation could potentially affect the myosin ATPase cycle. CONCLUSIONS: We report a novel likely pathogenic missense (c.2063 A > G) variant within of MYO6 in patients with DFNA22. Our findings expand the variant spectrum of MYO6 and ADNSHL in Chinese individuals, which will facilitate early clinical genetic diagnosis and accurate genetic counselling of patients.