PDF(Pubmed)
Abstract：
The MYO7A gene is known to be responsible for both syndromic hearing loss (Usher syndrome type1B:USH1B) and non-syndromic hearing loss including autosomal dominant and autosomal recessive inheritance (DFNA11, DFNB2). However, the prevalence and detailed clinical features of MYO7A-associated hearing loss across a large population remain unclear. In this study, we conducted next-generation sequencing analysis for a large cohort of 10,042 Japanese hearing loss patients. As a result, 137 patients were identified with MYO7A-associated hearing loss so that the prevalence among Japanese hearing loss patients was 1.36%. We identified 70 disease-causing candidate variants in this study, with 36 of them being novel variants. All variants identified in autosomal dominant cases were missense or in-frame deletion variants. Among the autosomal recessive cases, all patients had at least one missense variant. On the other hand, in patients with Usher syndrome, almost half of the patients carried biallelic null variants (nonsense, splicing, and frameshift variants). Most of the autosomal dominant cases showed late-onset progressive hearing loss. On the other hand, cases with autosomal recessive inheritance or Usher syndrome showed congenital or early-onset hearing loss. The visual symptoms in the Usher syndrome cases developed between age 5-15, and the condition was diagnosed at about 6-15 years of age.
摘要：
已知MYO7A基因负责综合征性听力损失（Usher综合征type1B：USH1B）和非综合征性听力损失，包括常染色体显性遗传和常染色体隐性遗传（DFNA11，DFNB2）。然而,大量人群中MYO7A相关听力损失的患病率和详细临床特征尚不清楚.在这项研究中,我们对1,042例日本耳聋患者的大型队列进行了新一代测序分析.因此,137名患者被确定为MYO7A相关听力损失，因此日本听力损失患者的患病率为1.36％。我们在这项研究中确定了70种致病候选变异，其中36个是新颖的变体。在常染色体显性病例中鉴定的所有变异都是错义或框内缺失变异。在常染色体隐性遗传病例中，所有患者至少有一个错义变异.另一方面,在Usher综合征患者中，几乎一半的患者携带双等位基因无效变异体(无意义，拼接,和移码变体)。大多数常染色体显性遗传病例表现为迟发性进行性听力损失。另一方面,常染色体隐性遗传或Usher综合征的病例表现为先天性或早发性听力损失。Usher综合征病例的视觉症状在5-15岁之间发展，该病在6-15岁左右被诊断出来。
