家族性渗出性玻璃体视网膜病变患者LRP5基因突变研究

发布时间：2018-04-03 14:42

本文选题：家族性渗出性玻璃体视网膜病变　切入点：低密度脂蛋白受体相关蛋白　出处：《遗传》2017年03期

【摘要】：家族性渗出性玻璃体视网膜病变(familial exudative vitreoretinopathy,FEVR)是一种遗传性眼科疾病,主要特征为视网膜周边血管发育异常和病变。由于病变程度不同,临床表型可从无明显症状到眼睛完全失明。本文通过研究3个中国FEVR家系和1个散发型患者,探索其致病突变与疾病表型之间的关系。收集家系中患者及亲属的外周血制备基因组DNA,设计引物以扩增FEVR致病基因FZD4、LRP5、NDP和TSPAN12的外显子区域并通过Sanger法进行测序。结果发现,在LRP5基因上存在3个未在db SNP数据库及千人基因组计划数据库中报道过的杂合突变p.M181R、p.R399S和p.G503R,以及2个已发现但未在FEVR中报道过的杂合突变p.R494Q和p.G876S。生物信息学分析表明这5个突变位点均高度保守,为有害突变。荧光素酶报告基因实验证明了这5个突变均不能激活Norrin/β-catenin信号通路,进一步证明了这5个突变的致病性。该研究扩充了我国FEVR疾病的遗传数据库,可为该疾病的分子诊断提供依据。
[Abstract]:Familial exudative vitreoretinopathy (FEV) is a hereditary ophthalmic disease characterized by abnormal development and pathological changes of peripheral retinal vessels.Clinical phenotypes can range from asymptomatic to completely blind due to varying degrees of disease.Three Chinese FEVR families and one sporadic patient were studied to explore the relationship between pathogenicity mutation and disease phenotype.The results showed that there were three heterozygous mutations, p.M181RN, p.R399S and p.G503R, which were not reported in db SNP database and 1000 human genome project database, and two heterozygous mutations, p.R494Q and p.G876S, which had been found but not reported in FEVR.Bioinformatics analysis showed that the five mutation sites were highly conserved and were harmful mutations.Luciferase reporter gene experiments showed that none of the five mutations could activate the Norrin/ 尾 -catenin signaling pathway, and further demonstrated the pathogenicity of the five mutations.This study expands the genetic database of FEVR disease in China and provides the basis for the molecular diagnosis of the disease.
【作者单位】：电子科技大学医学院电子科技大学附属医院四川省人民医院人类疾病基因研究四川省重点实验室;四川省医学科学院四川省人民医院实验动物研究所;中国科学院成都生物研究所;上海交通大学医学院附属新华医院眼科学系;
【基金】：国家自然科学基金项目(编号:81470668,81271007) 四川省科技厅项目(编号:2014JQ0023,2016TD0009)资助~~
【分类号】：R774.1

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