家族性渗出性玻璃体视网膜病变（Familial exudative vitreoretinopathy, FEVR)是一种遗传性视网膜周边血管发育异常的疾病。迄今为止鉴定了6个FEVR致病基因，其中4个基因NDP, FZD4, LRP5和TSPAN12在Wnt信号通路上。FEVR基因相同突变在同一家系中的临床症状异质性明显，发病年龄以婴幼儿为主，无早期的有效治疗方法。我们推测在FEVR家系中，尚存在新的修饰基因，导致其临床表型异质性。为寻找FEVR的修饰基因，我们收集了FEVR家系进行突变筛查，并对其中筛查到已知基因突变的100个家系进行了全外显子组测序和数据分析。本项目拟研究在此基础上鉴定的FEVR修饰基因，联合FZD4, LRP5和TSPAN12， 研究其对Wnt信号通路的影响，通过体内和体外实验研究其功能，探索其分子机制和调节FEVR表型的疾病机理。

Familial exudative vitreoretinopathy (FEVR) is a monogenic disorder, characterized by abnormal development of retinal peripheral vasculature. Mutations in six genes can cause this disease. Four of these six genes can form a complex and participate the Wnt pathway. This disease is of clinical and genetical heterogeneity, and most of cases are infants or children. The same mutation in their parents always causes very light phenotype. There is no effective treatment for this disease yet. We speculate that there exist new genetic modifiers causing FEVR within families with phenotype heterogeneity. In order to discover and identify novel FEVR genetic modifiers, we have recruited FEVR pedigrees and done mutation screening. We selected 100 pedigrees, detected FEVE genes’mutations, and did whole exome sequencing to discover FEVR modifiers. We plan to identify the genetic modifiers for the families and perform functional studies in vitro (using biochemistry and cell biology methods) and in vivo (using mouse models).