Department of Otolaryngology, The 4th Medical Center, Chinese PLA General Hospital, Beijing, China.
Department of Otorhinolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China.
Mol Genet Genomic Med. 2020 Dec;8(12):e1520. doi: 10.1002/mgg3.1520. Epub 2020 Oct 12.
Waardenburg syndrome (WS) is a highly clinically and genetically heterogeneous disease. The core disease phenotypes of WS are sensorineuronal hearing loss and pigmentary disturbance, which are usually caused by the absence of neural crest cell-derived melanocytes. At present, four subtypes of WS have been defined, which are caused by seven genes. Waardenburg syndrome type 2 (WS2) is one of the most common forms. Two genes, MITF and SOX10, have been found to be responsible for majority of WS2.
In this study, we performed a clinical longitudinal follow-up and mutation screening for a Chinese family with Waardenburg syndrome type II.
A diversity of clinical manifestations was observed in this WS2 family. In addition to the congenital hearing loss of most affected family members, progressive hearing loss was also found in some WS2 patients. A nonsense mutation of c.328C>T (p.R110X) in MITF was identified in all affected family members. This mutation results in a truncated MITF protein, which is considered to be a disease-causing mutation.
These findings offer a better understanding of the spectrum of MITF mutations and highlight the necessity of continuous hearing assessment in WS patients.
瓦登伯格综合征（WS）是一种高度临床和遗传异质性疾病。WS 的核心疾病表型是感觉神经性听力损失和色素紊乱，通常由缺乏神经嵴细胞衍生的黑素细胞引起。目前已经定义了四种 WS 亚型，它们由七个基因引起。WS2 是最常见的类型之一。MITF 和 SOX10 两个基因被发现与大多数 WS2 有关。
本研究对一个中国 WS2 家族进行了临床纵向随访和突变筛查。
该 WS2 家族表现出多种临床表现。除了大多数受影响家庭成员的先天性听力损失外，一些 WS2 患者还发现了进行性听力损失。在所有受影响的家庭成员中均发现了 MITF 基因 c.328C>T（p.R110X）的无义突变。该突变导致 MITF 蛋白截断，被认为是一种致病突变。
这些发现更好地理解了 MITF 突变谱，并强调了在 WS 患者中进行持续听力评估的必要性。
