Chai Yongchuan, Chen Dongye, Wang Xiaowen, Wu Hao, Yang Tao
Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Int J Pediatr Otorhinolaryngol. 2014 Aug;78(8):1265-8. doi: 10.1016/j.ijporl.2014.05.007. Epub 2014 May 21.
Mutations in DFNA5 may lead to autosomal dominant non-syndromic sensorineural hearing loss (NSHL). To date, only four DFNA5 mutations have been reported, all resulting in skipping of exon 8 at the mRNA level. In this study, we aim to characterize the clinical features and the genetic cause of a Chinese DFNA5 family.
Targeted next-generation sequencing of 79 known deafness genes was performed in the proband. Co-segregation between the disease phenotype and the potentially pathogenic variant was confirmed in all family members by Sanger sequencing.
A novel heterozygous c.991-2A>G mutation in DFNA5 was identified in this family segregating with the autosomal dominant, late-onset NSHL. This mutation was located in the conventional splice site in intron 7 and was likely to result in skipping of exon 8. The severity of hearing impairment varied intrafamilially.
We identified a novel c.991-2A>G mutation in DFNA5 which again may lead to exon 8 skipping at the mRNA level. Our findings supported that the DFNA5-associated NSHL results from a specific gain-of-function mechanism.
DFNA5基因突变可能导致常染色体显性非综合征性感音神经性听力损失（NSHL）。迄今为止，仅报道了4种DFNA5基因突变，所有这些突变在mRNA水平上均导致外显子8跳跃。在本研究中，我们旨在描述一个中国DFNA5家系的临床特征和遗传病因。
对先证者进行79个已知耳聋基因的靶向二代测序。通过Sanger测序在所有家庭成员中确认疾病表型与潜在致病变异之间的共分离。
在该家系中鉴定出一种新的DFNA5杂合c.991-2A>G突变，其与常染色体显性迟发性NSHL共分离。该突变位于内含子7的常规剪接位点，可能导致外显子8跳跃。听力损害的严重程度在家族内部有所不同。
我们在DFNA5中鉴定出一种新的c.991-2A>G突变，该突变可能再次导致mRNA水平上的外显子8跳跃。我们的研究结果支持与DFNA5相关的NSHL是由特定的功能获得机制引起的。
