GJA8基因错义突变致先天性白内障一家系遗传分析  

Genetics Analysis in a Congenital Cataract Pedigree Associated with a Missense Mutation in GJA8 gene

作　　者：孔艳波[1] 易浩安 马敏俊 吴国玖[1] 凡心玉 李凡 何永蜀[2] 查旭[1] KONG Yanbo;YI Haoan;MA Minjun;WU Guojiu;FAN Xinyu;LI Fan;HE Yongshu;ZHA Xu(Dept.of Ophthalmology,The 2nd Affiliated Hospital of Kunming Medical University,Kunming Yunnan 650101;Dept.of Cell Biology and Medical Genetics,Kunming Medical University,Kunming Yunnan 650500;The Medical school,Yunnan University,Kunming Yunnan 650500,China)

机构地区：[1]昆明医科大学第二附属医院眼科,云南昆明650101 [2]昆明医科大学细胞生物学与医学遗传学系,云南昆明650500 [3]云南大学医学院,云南昆明650500

出　　处：《昆明医科大学学报》2022年第3期27-31,共5页Journal of Kunming Medical University

基　　金：云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目(2019FE001(-70));昆明医科大学第二附属医院院内科研项目(2020yk001)。

摘　　要：目的通过使用外显子测序定位分析一先天性白内障家系中GJA8基因致病错义突变。方法对2020年6月在昆明医科大学第二附属医院就诊的一个先天性白内障家系全体成员进行详细的临床眼科检查及全身查体。采集先证者及6个亲属外周血并提取基因组DNA,应用全外显子测序筛查可疑致病基因,使用生物信息工具对可疑基因突变进行致病性分析,并对家系全部成员进行Sanger测序验证候选致病突变。结果外显子测序及生物信息学分析显示GJA8基因存在一个错义突变c.593G>A,p.R198Q,导致其第198位氨基酸残基由谷氨酰胺取代了原有的脯氨酸。氨基酸保守性分析显示该突变影响的氨基酸在物种间高度保守。在家系全部受检者中进行的Sanger测序结果表明该突变与疾病表型共分离,可以认定该突变是该突变为该家系的致病性突变,系谱分析显示该突变所致先天性白内障呈现常染色体显性遗传。结论位于GJA8基因的错义突变c.593G>A,p.R198Q是导致该家系出现先天性白内障的遗传病因,遗传方式为常染色体显性遗传。Objective To analyze the clinical manifestations in a congenital cataract pedigree and the genetic etiology was identified using exon sequencing.Methods A family with congenital cataract admitted to the Second Affiliated Hospital of Kunming Medical University in June 2020.A comprehensive ophthalmological examination and physical examination was conducted with the family members.Peripheral blood from proband and 6 relatives were collected,and genomic DNA was extracted.The potential pathogenic genes were screened by whole exome sequencing,pathogenicity analysis of suspected gene mutations was performed using bioinformatics tools,and the mutations were identified using Sanger sequencing in all pedigree members.Results A missense mutation c.593 G>A,p.R198 Q was identified in GJA8 gene by Exon sequencing and bioinformatics analysis.The GJA8 gene is one of gene family encoding gap junction protein.The amino acids affected by this mutations site are highly conserved between species and the mutation was considered pathogenic according to the Guidelines of the American College of Medical Genetics and Genomics(ACMG).Sanger sequencing results in all in the family showed that the proband and other patients with congenital cataract all carried the mutation,while the mutation was not detected in healthy people in the family,and the mutation was co-separated with the disease phenotype,presenting autosomal dominant inheritance.Conclusions Our study shows that missense mutation c.593G>A,p.R198Q located in the GJA8 gene is the genetic cause of congenital cataract in this family,and the inheritance mode is autosomal dominant inheritance.

关 键 词：先天性白内障 GJA8基因 错义突变 家系 

分 类 号：R776.1[医药卫生—眼科]