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。临床症状异质性明显,从无症状到致盲，发病年龄以婴幼儿为主，无早期有效的治疗方法。目前发现有4个基因（NPD,FZD4,LRP5,TSPAN12）的突变可以引起FEVR， 且这4个基因可形成一个复合体（Complex）参与Wnt相关的信号调节。但已知4个FEVR基因上的突变只能解释50-60%的FEVR病例。我们收集了98个FEVR显性遗传家系，排除FEVR已知基因编码区突变的基础后，进行了20个家系的全基因外显子测序。现在正对候选基因进一步分析，并在其他家系验证。本研究拟在此基础上确定FEVR致病新基因，并通过基因的功能分析，研究FEVR的致病机制。功能学研究主要包括体外（生物化学，细胞生物学）和体内（斑马鱼和小鼠动物模型）功能研究。

Familial exudative vitreoretinopathy (FEVR) is a monogenic disorder, characteristic as abnormal development of retinal peripheral vascular. This disease is clinicalLy and genetically heterogeneity, and most of cases are infants or children. There is no effective treatment for this disease yet. Mutations in four genes, including NDP, FZD4, LRP5 and TSPAN12, can cause this disease. These four genes can form a complex and participate the Wnt pathway. But the mutations in these four genes could only explain 50-60% cases with FEVR. We have collected 98 families with FEVR in an autosomal dominant form. Twenty of these families were undergone whole exome sequencing analysis after exclusion of mutations in the coding region of the four known FEVR genes. The candidate genes identified based on the exome sequencing analysis were verified by other cases with FEVR. We plan to identify the disease genes for the families and perform functional studies in vitro (using biochemistry and cell biology methods) and in vivo (using zebrahish and mouse models).