A Novel Spontaneous Mutation of the SOX10 Gene Associated with Waardenburg Syndrome Type II
A Novel Spontaneous Mutation of the SOX10 Gene Associated with Waardenburg Syndrome Type II
复制标题
与 II 型瓦登堡综合征相关的 SOX10 基因的新型自发突变
DOI：
10.1155/2020/9260807
复制
发表时间：
2020-08-28
影响因子：
3.1
通讯作者：
Sun, Yu
中科院分区：
文献类型：
--
作者：
Chen, Sen;Jin, Yuan;Sun, Yu
Waardenburg综合征(WS)，又称听色素综合征，是导致综合征性听力损失的最常见原因。先天性耳聋有2%-5%是由它引起的。WS根据临床表型分为四种类型。目前，PAX3、MITF、EDNRB、EDN3、SNAI2或SOX10的致病突变可引起相应类型的WS。其中，SOX10突变约占II型WS的15%或IV型WS的50%。我们报告了一个中国先证者被诊断为WS II型的病例。对先证者的全外显子测序(WES)发现了一个新的杂合性自发突变：SOX10c.246delC。根据核酸和氨基酸序列的分析，该突变可能产生一个截短的蛋白质，伴随着HMG结构域的缺失。因此，这种截短的蛋白可能无法激活MITF基因的表达，MITF基因调节黑素细胞的发育，在WS中发挥关键作用。我们的发现扩展了与WS相关的SOX10突变的数据库，并提供了更多关于WS的分子机制的信息。
Waardenburg syndrome (WS), also known as auditory-pigmentary syndrome, is the most common cause of syndromic hearing loss. It is responsible for 2-5% of congenital deafness. WS is classified into four types depending on the clinical phenotypes. Currently, pathogenic mutation ofPAX3,MITF,EDNRB,EDN3,SNAI2, orSOX10can cause corresponding types of WS. Among them,SOX10mutation is responsible for approximately 15% of type II WS or 50% of type IV WS. We report the case of a proband in a Chinese family who was diagnosed with WS type II. Whole exome sequencing (WES) of the proband detected a novel heterozygous spontaneous mutation:SOX10c.246delC. According to analysis based on nucleic acid and amino acid sequences, this mutation may produce a truncated protein, with loss of the HMG structure domain. Therefore, this truncated protein may fail to activate the expression of theMITFgene, which regulates melanocytic development and plays a key role in WS. Our finding expands the database ofSOX10mutations associated with WS and provides more information regarding the molecular mechanism of WS.