Niu Zhijie, Yan Denise, Bressler Sara, Mei Lingyun, Feng Yong, Liu Xuezhong
Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Int J Pediatr Otorhinolaryngol. 2018 Jan;104:47-50. doi: 10.1016/j.ijporl.2017.10.040. Epub 2017 Nov 2.
X-linked nonsyndromic hearing impairment is the rarest form of genetic hearing loss and represents only a minor fraction of all cases. The aim of this study was to investigate the cause of X-linked nonsyndromic sensorineural hearing loss in a three-generation American family.
Whole-exome sequencing and co-segregation analysis were used to identify disease-causing genes.
In this study, we described in detail the clinical characteristics of the family and identified a novel frameshift mutation creating a premature stop codon (c.133-1 G > A, p.(Gly45fs*36)) of SMPX. The loss-of-function mutation was co-segregated with the progressive hearing loss phenotype and was absent in 200 normal controls.
We report the first SMPX (DFNX4) mutation in a North American family. Our findings contribute to the existing genotypic and phenotypic spectrum of SMPX associated hearing loss. Furthermore, our data suggest that exome sequencing is promising in the genetic diagnosis of hearing loss.
X连锁非综合征性听力障碍是遗传性听力损失中最罕见的形式，仅占所有病例的一小部分。本研究的目的是调查一个三代美国家庭中X连锁非综合征性感音神经性听力损失的病因。
采用全外显子组测序和共分离分析来鉴定致病基因。
在本研究中，我们详细描述了该家庭的临床特征，并鉴定出一个新的移码突变，该突变导致SMPX基因产生一个提前终止密码子（c.133-1 G>A，p.(Gly45fs*36)）。功能丧失突变与进行性听力损失表型共分离，在200名正常对照中未出现。
我们报道了北美家庭中的首例SMPX（DFNX4）突变。我们的发现丰富了与SMPX相关听力损失的现有基因型和表型谱。此外，我们的数据表明外显子组测序在听力损失的基因诊断中具有广阔前景。
