COL4A1基因突变导致1例先天性白内障合并全身多系统疾病的研究  

A novel COL4A1 gene mutation results in congenital cataract with multisystem disorders in a Chinese family

作　　者：杨振菲 佘重阳 云波[3] 李乾 YANG Zhenfei;SHE Chongyang;YUN Bo;LI Qian(Department of Ophthalmology,Rehabilitation Hospital Affiliated to National Research Center for Rehabilitation Technical Aids,Beijing 100176,China;Department of Ophthalmology,Beijing Chao-Yang Hospital,Capital Medical University,Beijing 100020,China;Beijing Tongren Eye Center,Beijing Tongren Hospital,Capital Medical University,Beijing 100005,China;Department of Genetics,National Research Institute for Family Planning,Beijing 100081,China)

机构地区：[1]国家康复辅具研究中心附属康复医院眼科,北京100176 [2]首都医科大学附属北京朝阳医院眼科,北京100020 [3]首都医科大学附属北京同仁医院眼科,北京100005 [4]国家卫生健康委科学技术研究所/国家人类遗传资源中心,北京100081

出　　处：《中国优生与遗传杂志》2024年第5期996-1000,共5页Chinese Journal of Birth Health & Heredity

摘　　要：目的通过对一名4岁患有先天性白内障且合并多系统疾病患儿使用全外显子组测序定位分析其基因突变位点。方法对此女童及家庭成员进行详细的眼科临床检查及全身查体。采集该患儿及亲属外周血并提取基因组DNA,应用全外显子组测序定位筛查可疑致病基因,并对全部成员进行Sanger测序验证候选致病突变位点。结果经过眼科及全身查体,此4岁患儿患有先天性后囊下型白内障合并脑白质病变,肌酸激酶增高。经过全外显子组测序及生物信息学分析,在这名女童COL4A1基因中发现了一个新的致病基因突变(c.2947-c.2964dupGCAGGACAGCCTGGGCAG),此突变导致在COL4A1基因外显子中插入6个氨基酸(Ala-Gly-Gln-Pro-Gly-Gln)。结论COL4A1基因突变(c.2947-c.2964dupGCAGGACAGCCTGGGCAG)是导致该患儿发生先天性白内障合并全身系统疾病的可能致病基因突变。本研究也进一步证实了COL4A1基因在晶状体、脑白质和肌病中的重要作用。Objective To identify the disease-causing mutation in a Chinese girl with congenital cataract and multisystem disorders.Methods Whole-exome sequencing was performed to detect the causative gene mutation in a Chinese girl with congenital cataract and multisystem disorders,followed by Sanger sequencing.Results We identified a novel mutation(c.2947-c.2964dupGCAGGACAGCCTGGGCAG)in COL4A1,which was a de novo mutation.The mutation was predicted to insert 6 amino acids(Ala-Gly-Gln-Pro-Gly-Gln)in the collagenous domains of type IV.Conclusion The novel mutation(c.2947-c.2964dupGCAGGACAGCCTGGGCAG)was predicted the cause of the congenital cataract with epilepsy and elevated creatine kinase level.This study highlights the important role of type IV collagen in the physiological conditions of the lens,brain white matter,and myopathy.

关 键 词：先天性白内障 COL4A1 脑白质病变 肌酸激酶 多系统疾病 

分 类 号：R776.1[医药卫生—眼科] R725.9[医药卫生—临床医学]