Li Wu, Feng Yong, Chen Hongsheng, He Chufeng, Mei Lingyun, Liu Xue Zhong, Men Meichao
Department of Otolaryngology, Xiangya Hospital.
Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University.
Otol Neurotol. 2020 Dec;41(10):e1250-e1255. doi: 10.1097/MAO.0000000000002821.
Waardenburg syndrome (WS) is a rare disorder characterized by varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. Dystopia canthorum is a hallmark of WS type 1. There are two genes linked to WS type 1, including PAX3 and EDNRB.
This study aimed to investigate the genetic etiology of WS type 1 in a pair of twins from China with profound hearing loss, blond hair and eyebrows, dystopia canthorum, and brown irides.
The target capture sequencing and Whole-exome sequencing were performed to detect mutations in WS-related genes.
A novel de novo frameshift mutation, p.L341Rfs*18 in MITF was identified in the twins. Hearing thresholds showed substantial improvements following cochlear implantation with a pure-tone average of 30 dB in free-field conditions.
The study showed the new genotype-phenotype correlations of MITF to WS type 1. Further molecular analysis is necessary to reappraise the current classification on WS.
瓦登伯革氏综合征（WS）是一种罕见的疾病，其特征为感音神经性听力损失以及毛发和皮肤色素沉着异常的不同组合。根据其他症状，WS被分为四种亚型（WS1-WS4）。内眦异位是1型WS的一个标志。有两个基因与1型WS相关，包括PAX3和EDNRB。
本研究旨在调查一对来自中国的双胞胎的1型WS的遗传病因，这对双胞胎患有严重听力损失、金色头发和眉毛、内眦异位以及褐色虹膜。
进行目标捕获测序和全外显子组测序以检测WS相关基因中的突变。
在这对双胞胎中鉴定出一种新的从头发生的移码突变，即MITF基因中的p.L341Rfs*18。人工耳蜗植入后听力阈值有显著改善，自由场条件下纯音平均听阈为30dB。
该研究显示了MITF与1型WS的新的基因型-表型相关性。有必要进行进一步的分子分析以重新评估目前对WS的分类。
