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

Autor: Wang Y; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Liu Z; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Li Y; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Nie Z; Institute of Genetics, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China., Xu B; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Zhu Y; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Duan S; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Chen X; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Tan H; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Dang J; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Guan M; Institute of Genetics, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China., Guo Y; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2024 Dec; Vol. 12 (12), pp. e70042.
DOI: 10.1002/mgg3.70042
Abstrakt: 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.
(© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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