高通量测序技术在先天性上睑下垂家系致病基因检测中的应用价值  

Application value of high-throughput sequencing technology in detecting pathogenic genes of congenital ptosis family

作　　者：车选义[1] 杨燕[1] 刘晓梅[1] 李迪[1] CHE Xuanyi;YANG Yan;LIU Xiaomei(Shaanxi Provincial People's Hospital(Affiliated Hospital of Xi'an Medical College),Xi'an 710068)

机构地区：[1]陕西省人民医院(西安医学院附属医院)

出　　处：《陕西医学杂志》2020年第2期201-204,共4页Shaanxi Medical Journal

基　　金：陕西省自然科学基础研究计划项目(2017JM8125)

摘　　要：目的:探讨应用高通量测序技术检测先天性上睑下垂家系中致病基因的价值。方法:采用高通量测序技术对先证者进行致病基因检测,获取致病基因突变位点,通过Sanger测序对高度可疑的位点进行测序验证。通过Sanger法对家系成员及100例正常对照者进行基因检测。结果:采用高通量测序技术测得先证者上睑下垂相关转录基因FOXL2基因发生c.578A>G错义突变,导致密码子由AAG突变为AGG,第193位的赖氨酸突变为精氨酸。采用Sanger测序法检测发现该家系所有患者均携带FOXL2基因c.578A>G错义突变,但家系中表型正常者及100例正常对照者的FOXL2基因c.578均为野生型,未发现突变。结论:该家系致病基因为FOXL2基因发生c.578A>G错义突变,高通量测序技术可用于先天性上睑下垂基因突变的快速检测,对先天性上睑下垂的产前诊断和遗传咨询有一定意义。Objective:To detect the pathogenic gene in congenital ptosis family with high-throughput sequencing technology.Methods:High-throughput sequencing technology was used to detect the pathogenic gene of the prover for obtaining the mutation sites of the pathogenic gene,and Sanger sequencing was performed to verify the highly suspicious sites.Genetic testing was performed on family members and 100 normal controls by Sanger method.Results:By using high-throughput sequencing technology,the missense mutation of c.578A>G in the FOXL2 gene related to transcription of ptosis in prover was found,which caused the codon to mutate from AAG to AGG,and lysine at position 193 to arginine.Sanger sequencing was used to detect that all patients in the family carried the missense mutation of c.578A>G in FOXL2 gene,but that of normal phenotypes and 100 normal controls was wild type,and no mutation was found.Conclusion:The pathogenic gene of this family is c.578A>G missense mutation in FOXL2 gene.High-throughput sequencing technology can be used for rapid detection of congenital ptosis gene mutation,prenatal diagnosis and genetic counseling for congenital ptosis.

关 键 词：高通量测序技术 Sanger测序 先天性上睑下垂 致病基因 错义突变 遗传 

分 类 号：R777.1[医药卫生—眼科]