Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Department of Hearing Implant Sciences, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Genes (Basel). 2019 Sep 23;10(10):735. doi: 10.3390/genes10100735.
Variants of the gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8074 Japanese hearing loss patients utilizing massively parallel DNA sequencing to identify individuals with variants and to assess their phenotypes. A total of 28 affected individuals and 21 variants were identified, among which 13 were novel variants. A recurrent variant c.4212 + 1G > A, only reported in Japanese patients, was detected in 18 individuals. Haplotype analysis implied that this variation occurred in a mutational hot spot, and that multiple ancestors of Japanese population had this variation. Patients with variations mostly showed early onset hearing loss and presented different progression rates. We speculated that the varying severities and progression rates of hearing loss are the result of environmental and/or other genetic factors. No accompanying symptoms, including vestibular dysfunction, with hearing loss were detected in this study. Few studies have reported the clinical features of -gene associated hearing loss, and this study is by far the largest study focused on the evaluation of this gene.
该基因的变异体在耳蜗和前庭的毛细胞中表达，已被报道可引起常染色体隐性非综合征遗传性听力损失的进行性形式，即 DFNB77。在这项研究中，利用大规模平行 DNA 测序对 8074 名日本听力损失患者进行了基因筛查，以鉴定携带变异体的个体并评估其表型。共鉴定出 28 名受影响个体和 21 个变异体，其中 13 个是新的变异体。在 18 名个体中检测到一种仅在日本患者中报道的常见变异 c.4212 + 1G > A。单倍型分析表明，这种变异发生在突变热点，并且日本人群的多个祖先都具有这种变异。携带 变异体的患者大多表现为早发性听力损失，并呈现不同的进展速度。我们推测听力损失的严重程度和进展速度的差异是环境和/或其他遗传因素的结果。本研究未检测到听力损失伴随的任何伴随症状，包括前庭功能障碍。很少有研究报道 - 基因相关听力损失的临床特征，而这项研究是迄今为止针对该基因评估的最大规模研究。
