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

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2024-12-01 DOI:10.1002/mgg3.70042

Yanli Wang, Zengping Liu, Yong Li, Zhipeng Nie, Baicheng Xu, Yiming Zhu, Shihong Duan, Xingjian Chen, Huan Tan, Jiong Dang, Minxin Guan, Yufen Guo

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引用次数: 0

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.

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位于MYO15A n端区域的新突变导致感音神经性听力损失。

背景：MYO15A是重度至重度感音神经性耳聋的常见基因之一。该基因的突变可导致语前和语后听力损失。在这项研究中，一种新的MYO15A变异（c.2482C>T）被发现与中国维吾尔族家庭的常染色体隐性非综合征性听力损失（ARNSHL）相关。方法：研究MYO15A突变对毛细胞样细胞形态和功能的影响，分别从先证者和突变阴性的家族成员中产生两个iPSCs，然后将其诱导到毛细胞样细胞中。结果：结果显示，这个位于n端结构域的MYO15A纯合突变（PVS1 + PM2 + PP1 + PP3）在先显体和正常对照中表现出毛细胞样细胞的形态和功能上的显著差异，但对iPSCs的全能性没有影响。结论：我们的研究表明MYO15A基因的新变异c.2482C>T可能导致该家族的内耳毛细胞功能障碍和听力学障碍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.20

自引率

0.00%

发文量

241

审稿时长

14 weeks

期刊介绍： Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.