1个先天性白内障家系的致病基因鉴定及遗传学分析  

Genetic analysis and identification of pathogenic gene in a family affected with congenital cataracts

作　　者：钟焱 彭凤兰 ZHONG Yan;PENG Fenglan(Changsha Health Vocational College,Changsha,Hunan 410000,China)

机构地区：[1]长沙卫生职业学院,湖南长沙410000

出　　处：《中国优生与遗传杂志》2024年第2期347-351,共5页Chinese Journal of Birth Health & Heredity

基　　金：湖南省自然科学基金-科教联合项目(2019JJ70002)。

摘　　要：目的 对1个先天性白内障家系进行表型和基因分析,鉴别其致病基因,分析基因与家系异常表型的关系,为该家系的遗传咨询、诊断及治疗提供参考。方法 采集该家系成员的临床资料,诊断其白内障表型、绘制家系图、分析遗传方式。提取家系成员的外周血DNA,利用外显子组测序在先证者的基因组中寻找致病变异位点,利用多重连接依赖探针扩增技术筛查大片段缺失/插入;排除编码区变异、大片段缺失/插入与该家系的关系后,采用全基因组测序筛查该家系致病基因。结果 该家系22位成员参与临床检查,其中13人被诊断患有白内障,主要表现为眼部皮质混浊、核混浊、眼底窥不清等,年龄最大84岁,最小11岁。外显子组测序所得候选变异位点为COL7A1 c.6727T>C,但该变异在家系内未与疾病表型共分离;MLPA检测结果显示该家系在RHO、RP1、IMPDH1、PRPF31等4个基因不存在大片段缺失或重复;全基因组测序发现铁蛋白轻链亚基编码基因(FTL)5’-UTR区c.-168G>C(rs398124635)杂合变异,Sanger测序证明该变异位点在家系中与疾病表型共分离,Clinvar数据库评估该变异为有害变异。结论 该先天性白内障家系的遗传方式为常染色体显性遗传,FTL c.-168G>C为该先天性白内障家系的致病变异。Objective To identify the pathogenic gene of a family with congenital cataract,analyze the relationship between the mutation and abnormal phenotype of the family by phenotype and gene analysis,and provide reference for genetic counseling,diagnosis and treatment of the disease family.Methods Collect clinical data of the family members,diagnose their cataract phenotype,draw a family diagram,and analyze their genetic patterns.Whole exome analysis of ectopic sites in proband genome was performed by WES.Screen for deletions/duplications mutation were detected by MPLA test.After excluding the relationship between coding region variation,deletions/duplications mutation with the occurrence of family diseases,the screen of pathogenic genes in this family was completed by WGS.Results 22 members of the family participated in clinical examinations,and 13 members were diagnosed with cataracts,mainly manifested as cortical opacity,nuclear opacity,and unclear fundus vision.The maximum age was 84 years old and the minimum was 11 years old.Analysis of the WES data identified a candidate pathogenic variant in COL7A1c.6727T>C,but this variant was not complete co segregation with the phenotype in the pedigree.MLPA results displayed that the deletions/duplications mutation were not existed in RHO,RP1,IMPDH1,PRPF31 gene of this family.Analysis of WGS data identified the FTL c.-168G>C(rs398124635) variation located in 5'-UTR region of ferritin light chain sub-unit coding gene.Sanger sequencing demonstrated the heterozygous site was completely co-segregated with the phenotype in the pedigree.Evaluation analysis of Clinvar database suggested it's a harmful variation.Conclusion The genetic mode of this congenital cataract family was autosomal dominant inheritance,and FTL c.-168G>C mutation was the pathogenic variation for this congenital cataract family.

关 键 词：先天性白内障 铁蛋白 遗传性高铁蛋白血症白内障综合征 FTL 

分 类 号：R776.1[医药卫生—眼科]