Liang Fenghe, Zhao Min, Fan Lynn, Zhang Hongyan, Shi Yang, Han Rui, Qu Chunyan
Department of Otolaryngology-Head and Neck Surgery, Capital Medical University, Beijing Tongren Hospital, Beijing 100730, China.
China Rehabilitation and Research Center for Deaf Children, Beijing 100029, China.
Int J Pediatr Otorhinolaryngol. 2016 Dec;91:67-71. doi: 10.1016/j.ijporl.2016.10.019. Epub 2016 Oct 15.
Waardenburg syndrome is a rare genetic disorder, characterized by the association of sensorineural hearing loss and pigmentation abnormalities. Four subtypes have been classified. The present study aimed to analyze the clinical feature and investigate the genetic cause for a Chinese case of Waardenburg type IV (WS4).
The patient and his family members were subjected to mutation detection in the candidate gene SOX10 by Sanger sequencing.
The patient has the clinical features of WS4, including sensorineural hearing loss, bright blue irides, premature graying of the hair and Hirschsprung disease. A novel heterozygous frameshift mutation, c.752_753ins7 (p.Gly252Alafs*31) in the exon 5 of SOX10 was detected in the patient, but not found in the unaffected family members and 100 normal controls. This mutation results in a premature stop codon 31 amino acid downstream.
The novel mutation c.752_753ins7 (p.Gly252Alafs*31) arose de novo and was considered as the cause of WS4 in the proband. This study further characterized the molecular complexity of WS4 and provided a clinical case for genotype-phenotype correlation studies of different phenotypes caused by SOX10 mutations.
瓦登伯革氏综合征是一种罕见的遗传性疾病，其特征为感音神经性听力损失和色素沉着异常。该病已被分为四个亚型。本研究旨在分析一名中国IV型瓦登伯革氏综合征（WS4）患者的临床特征并探究其遗传病因。
采用桑格测序法对患者及其家庭成员的候选基因SOX10进行突变检测。
该患者具有WS4的临床特征，包括感音神经性听力损失、亮蓝色虹膜、头发过早变白和先天性巨结肠。在患者中检测到SOX10外显子5中的一个新的杂合移码突变，即c.752_753ins7（p.Gly252Alafs*31），但在未受影响的家庭成员和100名正常对照中未发现。该突变导致下游31个氨基酸处出现提前终止密码子。
新突变c.752_753ins7（p.Gly252Alafs*31）为新发突变，被认为是先证者患WS4的病因。本研究进一步明确了WS4的分子复杂性，并为SOX10突变所致不同表型的基因型-表型相关性研究提供了一个临床病例。
