晶状体蛋白截短导致先天性白内障的两个家系致病基因分析  

Analysis of pathogenic genes in two families with congenital cataract caused by protein truncation

作　　者：杨振菲 佘重阳 李乾 YANG Zhenfei;SHE Chongyang;LI Qian(Rehabilitation Hospital,National Research Center for Rehabilitation Technical Aids,Beijing,100176;Beijing Chao-Yang Hospital,Capital Medical University;National Research Institute for Family Planning)

机构地区：[1]国家康复辅具研究中心附属康复医院,北京100176 [2]首都医科大学附属北京朝阳医院 [3]国家卫生健康委科学技术研究所,国家人类遗传资源中心

出　　处：《中国计划生育学杂志》2023年第8期1884-1887,共4页Chinese Journal of Family Planning

摘　　要：目的:通过使用全基因组外显子测序确定两个先天性白内障家系的致病基因变异。方法:对2019-2020年在首都医科大学附属北京同仁医院就诊的2个先天性白内障家系部分成员进行详细的临床眼科检查及全身查体。采集先证者及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,并对家系全部成员进行Sanger测序验证候选致病变异位点。结果:经过外显子测序及生物信息学分析,家系1中在CRYBB1基因中存在无义变异c.656G>A,造成βB1晶状体蛋白质第219位色氨酸变异为终止密码子(p.W219X),最终产生晶状体蛋白截短。家系2中的发现在CRYGD基因中存在无义变异c.337C>T,造成γD晶状体蛋白质第113位谷氨酰胺变异为终止密码子(p.Q113X),导致晶状体蛋白截短。结论:位于CRYBB1基因的无义变异c.656G>A是导致家系1出现先天性白内障的病因;位于CRYGD基因的无义变异c.337C>T是导致家系2出现先天性白内障的病因。Objective:To identify virulence genovariation in two families with congenital cataract by exon sequencing.Methods:The detailed clinical ophthalmic examination and the general physical examination were performed in some members of 2 families with congenital cataract who were treated in Beijing Tongren Hospital,Capital Medical Univer-sity from 2019 to 2020.The peripheral blood of the probands and their relatives was ollected for extracting the genom-c DNA.Whole exon scquencing was used to screen the suspected pathogenic genes,and Sanger sequencing was used to verify the candidate pathogenic mutation sites of all the family members.Results:Exon sequencing and bioinformatics analysis showed that there was nonsense mutation of c.656G>A in CRYBB1 gene in family 1,which caused the tryp-tophan mutation at position 219 of CRYBB1 to become the termination codon(p.W219X),and finally produced the truncated crystallin.In family 2,the nonsense mutation of c.337C>T in CRYGD gene caused the tryptophan mutation at position at the 113th position of CRYGD to become a termination codon(p.Q113X),and which finally produced the truncated crystallin.Conclusion:The nonsense mutation of c.656G>A in CRYBB1 gene is the genetic cause of congen-ital cataract in family 1.The nonsense mutation of c.337C>T in CRYGD gene is the genetic cause of congenital cata-ract in family 2.

关 键 词：先天性白内障 晶状体蛋白CRYBB1 晶状体蛋白CRYGD 错义变异 蛋白截短 

分 类 号：R776.1[医药卫生—眼科]