位于MYO15A N端结构域的一种新型突变导致感音神经性听力损失。
A Novel Mutation Located in the N-Terminal Domain of MYO15A Caused Sensorineural Hearing Loss.
作者信息
Wang Yanli, Liu Zengping, Li Yong, Nie Zhipeng, Xu Baicheng, Zhu Yiming, Duan Shihong, Chen Xingjian, Tan Huan, Dang Jiong, Guan Minxin, Guo Yufen
机构信息
Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
Institute of Genetics, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China.
出版信息
Mol Genet Genomic Med. 2024 Dec;12(12):e70042. doi: 10.1002/mgg3.70042.
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.
背景
MYO15A是导致重度至极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。在本研究中，在中国维吾尔族一个家庭中鉴定出一种新的MYO15A变异体（c.2482C>T），其与常染色体隐性非综合征性听力损失（ARNSHL）相关。
方法
为了研究MYO15A突变对所衍生的毛细胞样细胞形态和功能的影响，分别从先证者和一名无突变的家庭成员中生成了两个诱导多能干细胞（iPSC），然后将它们诱导分化为毛细胞样细胞。
结果
结果显示，这种位于N端结构域的纯合MYO15A突变（PVS1+PM2+PP1+PP3），在先证者和正常对照之间的毛细胞样细胞形态和功能上表现出显著差异，尽管它对iPSC的全能性没有影响。
结论
我们的研究表明，MYO15A基因中的新变异体c.2482C>T可能导致该家庭的内耳毛细胞功能障碍和听力障碍。
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