先天性白内障家系LSS基因突变分析  

Mutation analysis of LSS gene in a family with congenital cataract

作　　者：邹茜 张骏 刘志南[1] 周栋[1] 张蓓[1] 江一[1] 邓国华[1] ZOU Xi;ZHANG Jun;LIU Zhinan(Department of Ophthalmology,Third People's Hospital of Changzhou,Changzhou 213000,CHINA)

机构地区：[1]常州市第三人民医院眼科,江苏213000

出　　处：《江苏医药》2023年第12期1207-1211,F0002,共6页Jiangsu Medical Journal

基　　金：常州市“龙城医星”卫生青年科技人才托举工程;常州市科技项目(CJ20220097、CE20225071);常州市卫健委科技项目(QN202129、ZD202120);常州市卫生健康青苗人才资助项目(CZQM2022017、CZQM2020091);南京医科大学常州医学中心科研创新一般项目(CMCB202225)。

摘　　要：目的分析1个先天性白内障家系的致病原因与羊毛甾醇合成酶(LSS)基因突变的关系。方法提取1个先天性白内障家系3例患者外周血DNA,采用PCR法扩增LSS基因的编码外显子区域,通过直接测序比较该家系患者与正常人序列差异以确定致病突变,并采用PolyPhen程序分析LSS基因突变引起的蛋白质结构和功能改变。结果LSS基因序列分析结果显示,该家系3例患者均存在2个错义突变和3个无义突变,错义突变分别位于LSS基因第4外显子的第44位碱基[c.44C>T(p.Pro 15 Leu)]和第20外显子的第107位碱基[c.107G>T(p.Cys 36 Phe)],无义突变分别位于LSS基因第5外显子的第96位碱基(c.96A>G)、第8外显子的第81位碱基(c.81C>G)和第23外显子的第156位碱基(c.156C>T)。经PolyPhen程序分析,LSS基因第20外显子的第107位碱基改变[c.107G>T(p.Cys 36 Phe)]可能导致LSS蛋白质结构或功能的破坏。结论LSS基因突变可能是该先天性白内障家系的致病突变。Objective To analyze the relationship of lanosterol synthase(LSS)gene mutation and pathogenesis in a Chinese family with congenital cataract.Methods The DNA in peripheral blood was extracted from three members of the family with congenital cataract.The coding exon of LSS gene was amplified by PCR,and the pathogenic mutation was confirmed by direct sequencing in comparison with healthy people.The protein structure and function changes caused by LSS gene mutation were analyzed by PolyPhen program.Results The sequence analysis of LSS gene showed that there were two missense mutations and three nonsense mutations in three patients.The missense mutations were c.44C>T(p.Pro 15 Leu)in the 44~(th)base of exon 4 and c.107G>T(p.Cys 36 Phe)in the 107~(th)base of exon 20 of LSS gene.The nonsense mutations were c.96A>G in the 96~(th)base of exon 5,c.81C>G in the 81~(st)base of exon 8 and c.156C>T in the 156~(th)base of exon 23 of LSS gene.According to the analysis of PolyPhen program,c.107G>T(p.Cys 36 Phe)in the 107~(th)base of exon 20 may lead to the destruction of structure and function of LSS protein.Conclusion LSS gene mutation might be the pathogenic mutation of this Chinese family with congenital cataract.

关 键 词：先天性白内障 羊毛甾醇合成酶 基因突变 

分 类 号：R776[医药卫生—眼科]