一个导致先天性白内障的CRYBA4基因新突变鉴定及产前诊断  

Identification of a novel CRYBA 4 mutation in a congenital cataract family and its prenatal diagnosis

作　　者：白周现 胡爽 梅世月[1] 刘宁[1] 孔祥东[1] 

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,450000

出　　处：《国际遗传学杂志》2017年第6期338-343,共6页International Journal of Genetics

基　　金：郑州大学第一附属医院院内青年创新基金（YNQN2017008）

摘　　要：目的 检测一个先天性白内障家系的致病基因突变,以此为依据进行该家系的产前诊断.方法 收集该家系患者和正常表型成员的临床资料,采集外周血提取基因组DNA,采集胎儿绒毛提取基因组DNA.应用高通量测序法筛查、Sanger测序法验证CRYBA 4基因新突变位点.在对照人群中筛查该突变.结果 该家系患者中存在CRYBA 4基因c.277 T〉C（p.Ser 93 Pro）错义突变,该突变导致其编码蛋白beta-crystallin A 4第93位氨基酸由丝氨酸变为脯氨酸（p.Ser93Pro）.在家系正常成员和831例对照人群中未检测到相同变异.该突变在ExAC、1000 G、dbSNP等数据库中未见报道.Mutation t@sting预测该突变为有害突变.结论 CRYBA4基因c.277T〉C（p.Ser93Pro）错义突变是该家系的致病原因,据此突变位点可进行产前诊断.Objective To identify the pathogenic mutation underlying congenital cataract in one family , and subsequently make a prenatal diagnosis on the basis of this mutation .Methods One nuclear family across three generations showing an autosomal dominant transmission of congenital cataract was exam -ined .Gene mutations were screened by using cataract gene panel sequencing through Ion PGM platform , and provided the selected mutation by PCR-Sanger sequencing method .Results We found a novel heter-ozygous missense mutation , c .277 T 〉C （ p .Ser 93 Pro ） , in CRYBA 4 .This mutation co-segregated with the cataract phenotype of all the family members but was not present in public databases （ ExAC , 1000 G and dbSNP ） and 831 control individuals .This mutation site was predicted to be disease causing by the tool of Mutation [e-mail] The c.277T 〉C（p.Ser93Pro） mutation in CRYBA4 is a no-vel pathogenic mutation for the cataract phenotype in this family .We can make a prenatal diagnosis of the proband on this basis .

关 键 词：先天性白内障 CRYBA4基因 致病突变 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学] R776.1[医药卫生—临床医学]