Gu Xiaodong, Sun Shan, Guo Luo, Lu Xiaoling, Mei Honglin, Lai Chuijin, Li Huawei
Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.
Research Center, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.
Int J Pediatr Otorhinolaryngol. 2015 Jun;79(6):817-820. doi: 10.1016/j.ijporl.2015.03.008. Epub 2015 Mar 18.
Autosomal recessive non-syndromic hearing loss (DFNB) is a genetically heterogeneous disorder. So far, 55 pathogenic genes have been identified. In this study, we aim to characterize the clinical feature and the genetic cause of a Chinese DFNB family.
Whole exome sequencing was performed on the proband. Co-segregation between the hearing loss phenotype and the potential causative mutations was verified in all family members by Sanger sequencing.
Audiologic profiles of the affected family members revealed a moderate hearing loss mainly affecting higher frequencies. Novel biallelic OTOGL mutations, c.6467C>A (p.Ser2156*) and c.6474dupA (p.Ser2159Metfs*2), were identified in this family segregating with the childhood onset DFNB. Both mutations were predicted to cause either nonsense mediated mRNA decay or premature terminations of protein synthesis.
We identified novel biallelic OTOGL mutations in a Chinese DFNB family. To the best of our knowledge, this is the first report of OTOGL mutations causing hearing loss in the East Asian population. Our finding enriched the mutation spectrum of OTOGL associated hearing loss.
常染色体隐性非综合征性听力损失（DFNB）是一种基因异质性疾病。迄今为止，已鉴定出55个致病基因。在本研究中，我们旨在明确一个中国DFNB家系的临床特征和遗传病因。
对先证者进行全外显子组测序。通过Sanger测序在所有家庭成员中验证听力损失表型与潜在致病突变之间的共分离情况。
受影响家庭成员的听力学特征显示为中度听力损失，主要影响高频。在该家系中鉴定出双等位基因OTOGL新突变，即c.6467C>A（p.Ser2156*）和c.6474dupA（p.Ser2159Metfs*2），与儿童期发病的DFNB共分离。这两个突变预计会导致无义介导的mRNA降解或蛋白质合成过早终止。
我们在一个中国DFNB家系中鉴定出双等位基因OTOGL新突变。据我们所知，这是东亚人群中OTOGL突变导致听力损失的首次报道。我们的发现丰富了与OTOGL相关听力损失的突变谱。
