Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Sci Rep. 2017 Jan 27;7:41513. doi: 10.1038/srep41513.
Waardenburg syndrome type 4 (WS4) or Waardenburg-Shah syndrome is a rare genetic disorder with a prevalence of <1/1,000,000 and characterized by the association of congenital sensorineural hearing loss, pigmentary abnormalities, and intestinal aganglionosis. There are three types of WS4 (WS4A-C) caused by mutations in endothelin receptor type B, endothelin 3, and SRY-box 10 (SOX10), respectively. This study investigated a genetic mutation in a Chinese family with one WS4 patient in order to improve genetic counselling. Genomic DNA was extracted, and mutation analysis of the three WS4 related genes was performed using Sanger sequencing. We detected a de novo heterozygous deletion mutation [c.1333delT (p.Ser445Glnfs*57)] in SOX10 in the patient; however, this mutation was absent in the unaffected parents and 40 ethnicity matched healthy controls. Subsequent phylogenetic analysis and three-dimensional modelling of the SOX10 protein confirmed that the c.1333delT heterozygous mutation was pathogenic, indicating that this mutation might constitute a candidate disease-causing mutation.
瓦登伯格综合征 4 型（WS4）或瓦登伯格-夏综合征是一种罕见的遗传疾病，患病率<1/1000000，其特征是先天性感觉神经性听力损失、色素异常和肠无神经节。有三种类型的 WS4（WS4A-C）分别由内皮素受体 B、内皮素 3 和 SRY 盒 10（SOX10）的突变引起。本研究通过 Sanger 测序对一个有一个 WS4 患者的中国家系进行了基因突变分析，以改善遗传咨询。提取基因组 DNA，对三个 WS4 相关基因进行突变分析。我们在患者中检测到 SOX10 中的一个新的杂合缺失突变[c.1333delT (p.Ser445Glnfs*57)]；然而，该突变在未受影响的父母和 40 名种族匹配的健康对照中均不存在。随后的 SOX10 蛋白系统发育分析和三维建模证实 c.1333delT 杂合突变是致病性的，表明该突变可能构成候选致病突变。
