COL4A1基因新变异导致脑小血管病伴或不伴眼部异常的遗传学研究  

Genetic study of small cerebral vascular disease with or without ocular abnormalities caused by novel COL4A1 gene variation

作　　者：张荣 孙晓慧 李艳涛[1] 贾世婧 耿韶辉[1] Zhang Rong;Sun Xiaohui;Li Yantao;Jia Shijing;Geng Shaohui(Department of Ophthalmology,the Fourth Hospital of Shijiazhuang,Shijiazhuang 050000,China;Department of Prenatal Diagnosis,the Fourth Hospital of Shijiazhuang,Shijiazhuang 050000,China)

机构地区：[1]石家庄市第四医院眼科,石家庄050000 [2]石家庄市第四医院产前诊断,石家庄050000

出　　处：《国际遗传学杂志》2025年第1期70-80,共11页International Journal of Genetics

基　　金：2024年度河北省医学科学研究课题计划(20241586)。

摘　　要：目的探讨COL4A1基因变异导致伴或不伴眼部异常脑小血管病Ⅰ型患者的临床表现及分子遗传学特点。方法采用家系调查研究,收集2022年9月于石家庄市第四医院出生1例病变累及眼、脑等多器官患儿的临床资料,对患儿及其父母行全基因组测序技术筛选出相关变异,通过Sanger测序对该变异位点进行验证,根据ACMG指南及生物在线软件对变异位点进行致病性评估。结合既往文献病例进行总结分析。结果全基因组测序技术发现患儿携带COL4A1基因c.2044G>C(p.Gly682Arg)错义变异。Sanger测序证实该变异在患儿父母外周血样本中未检出,提示为新发变异。根据ACMG临床指南判定该变异为疑似致病变异。与以往报道病例对比发现,患儿除有癫痫、脑室扩张、胼胝体发育不良、先天性白内障、先天性小眼球、胎儿生长受限、心肌酶谱异常等典型临床特征外,还表现出罕有的特征如小脑发育不良。结论COL4A1基因c.2044G>C错义变异可能是该疾病致病原因,对孕期出现胎儿脑室扩张、胼胝体发育不良、胎儿生长受限等,应尽早完善COL4A1基因检测。ObjectiveTo investigate the clinical manifestations and molecular genetic characteristics of type I patients with or without ocular abnormalities caused by COL4A1 gene variation.MethodsA family investigation study was conducted to collect clinical data of a child born in September 2022 in the Fourth Hospital of Shijiazhuang with lesions involving multiple organs such as eyes and brain.Whole genome sequencing was performed on the patient and his parents to select relevant variant,and the variant site was verified by Sanger sequencing.The pathogenicity of the variant sites was evaluated according to ACMG guidelines and bioonline software.Summarize and analyze the previous literature cases.ResultsWhole genome sequencing technology found that the patient carried COL4A1 gene c.2044G>C(p.Gly682Arg)missense variation.Sanger sequencing confirmed that the variant was not detected in the peripheral blood samples of the parents of the patient,suggesting that it was a new variant.According to ACMG clinical guidelines,this variant was identified as a suspected pathogenic variant.Compared with previously reported cases,it was found that in addition to typical clinical features such as epilepsy,ventricular dilatation,dysplasia of corpus callosum,congenital cataract,congenital microeyeball,fetal growth restriction,and abnormal myocardial enzyme profile,the patient also showed rare features such as cerebellar dysplasia.ConclusionsThe missense variation of COL4A1 gene c.2044G>C may be the cause of this disease.The detection of COL4A1 gene should be improved as soon as possible for fetal ventricular dilatation,corpus callosum dysplasia and fetal growth restriction during pregnancy.

关 键 词：COL4A1基因 伴或不伴眼部异常的脑小血管病Ⅰ型 先天性白内障 

分 类 号：R725.9[医药卫生—儿科]