Jin Yuan, Liu Xiaozhou, Zhang Qiong, Xiong Ying, Hu Yao, He Haixia, Chen Wei, Sun Yu
Department of Otorhinolaryngology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Biomedicines. 2024 Nov 21;12(12):2657. doi: 10.3390/biomedicines12122657.
Hearing loss (HL) is the most common disorder in newborns with a highly heterogeneous genetic background. Despite significant progress in screening and identifying genes related to congenital hearing loss, there are still candidate genes implicated in HL that remain undiscovered. We investigated HL in 43 Chinese families by segregating bilateral sensorineural HL via whole-exome sequencing (WES) and Sanger sequencing. Variants were found in 10 known non-syndromic hearing loss (NSHL) genes, 5 known syndromic hearing loss (SHL) genes, and 1 candidate HL gene, . RNA sequencing revealed mRNA expression in developing and adult cochleae. The immunohistochemistry of the adult mouse cochlear tissue revealed the prominent expression of ATP7B in the organ of Corti and the spiral ganglion neuron. Overall, we propose a new candidate gene, , for congenital hearing loss and novel variants in known HL genes, which expands our understanding of the etiology of HL. The next-generation sequencing could effectively improve the etiological diagnosis rate of congenital hearing loss in children.
听力损失（HL）是具有高度异质性遗传背景的新生儿中最常见的疾病。尽管在筛查和鉴定与先天性听力损失相关的基因方面取得了重大进展，但仍有一些与HL相关的候选基因未被发现。我们通过全外显子测序（WES）和桑格测序对43个中国家庭的双侧感音神经性HL进行了分离研究。在10个已知的非综合征性听力损失（NSHL）基因、5个已知的综合征性听力损失（SHL）基因和1个候选HL基因中发现了变异。RNA测序揭示了发育中和成年耳蜗中的mRNA表达。成年小鼠耳蜗组织的免疫组化显示ATP7B在柯蒂氏器和螺旋神经节神经元中显著表达。总体而言，我们提出了一个新的先天性听力损失候选基因，以及已知HL基因中的新变异，这扩展了我们对HL病因的理解。下一代测序可以有效提高儿童先天性听力损失的病因诊断率。
