Waardenburg综合征Ⅳ型患儿SOX10基因新突变研究

摘要

Objective To improve the disease causative gene mutation spectrum and provide new information for ge-netic counseling in Waardenburg syndrome type IV (WS4), we performed molecular genetic study in an isolated patient af-fected by WS4. Literature was reviewed for reported nonsense mutations in SOX10. Methods Detailed histories were col-lected through questionnaires and physical examination. Blood samples of the patient and her parents were collected after obtaining informed consents. Suspected mutations were amplified and verified by Sanger sequencing after the next genera-tion sequencing of 172 related genes. The raw data were analyzed using molecular biological websites and the GeneTool software. Results A new de novo heterozygous mutation (c.838G>T, p.E280X) in the fourth exon of SOX10 was found in the patient. Both parents were demonstrated to be wild-type and symptom free. Conclusions The novel mutation found in our study not only enriches the mutation spectrum but also is helpful for recurrent risk evaluation and genetic counseling for this family.%目的：通过分析研究一例Waardenburg综合征Ⅳ型（WS4）散发病例患儿的分子遗传学病因，丰富该致病基因突变谱，为WS4遗传咨询提供新的证据，并对该综合征相关的SOX10基因所有无义突变进行文献回顾和总结。方法收集一个WS4患儿的详细临床资料，签署知情同意书后获取血样，对包括SOX10、EDNRB、EDN3在内的172个先天性巨结肠及综合征相关基因进行二代测序，并用聚合酶链反应针对可疑致病突变进行扩增及Sanger测序验证，应用GeneTool软件及生物信息学网站的信息分析数据。结果发现患儿SOX10基因第4外显子存在一杂合无义突变(c.838G>T, p.E280X)，父母均表现正常且未发现有该突变。结论发现一新的SOX10基因致病突变，丰富了致WS4的SOX10基因突变谱，并为父母提供再生育患儿的风险评估及必要的产前诊断咨询。