A Novel Mutation Located in the N‐Terminal Domain of MYO15A Caused Sensorineural Hearing Loss

Abstract

ABSTRACT Background MYO15A is one of the common genes of severe‐to‐profound sensorineural deafness. Mutations in this gene can cause both pre‐ and post‐lingual hearing losses. In this study, a novel MYO15A variant (c.2482C>T) was identified to be associated with autosomal recessive non‐syndromic hearing loss (ARNSHL) in a Chinese Uighur family. Methods To examine the effects of the MYO15A mutation on the morphology and function of the derived hair cell‐like cells, two iPSCs were generated separately from the proband and a mutation‐negative family member and those were then induced to hair cell‐like cells. Results Results showed that this homozygous MYO15A mutation (PVS1 + PM2 + PP1 + PP3), which is located in the N‐terminal domain, displayed significant differences in the morphology and function of hair cell‐like cells between the proband and the normal control, although it had no effect on the totipotency of iPSCs. Conclusion Our study demonstrates that the novel variant c.2482C>T in the MYO15A gene may cause inner ear hair cell dysfunction and audiological disorders in this family.

Keywords

• deafness
• hair cell‐like cell
• induced pluripotent stem cells (iPSCs)
• MYO15A
• novel mutation