家族性渗出性玻璃体视网膜病变的遗传学研究进展

Advances in the genetics of familial exudative vitreoretinopathy

家族性渗出性玻璃体视网膜病变（FEVR）是以视网膜血管发育不全为特征的一类遗传性疾病。其遗传异质性较高，包括常染色体显性遗传、常染色体隐性遗传和X染色体连锁隐性遗传等多种遗传方式。目前为止发现有6个基因与其病变相关，分别是Wnt受体卷曲蛋白（FZD4）、Norrie病（NDP）、共受体低密度脂蛋白受体相关蛋白5（LRP5）、四旋蛋白12（TSPAN12）、锌指蛋白408（ZNF408）、驱动蛋白家族成员11（KIF11）基因。其中，FZD4、NDP、LRP5、TSPAN12等4个基因在Norrin/Frizzled4信号通路中发挥重要作用。在视网膜毛细血管内皮细胞中，Norrin通过激活Norrin/Frizzled4信号通路特异性控制眼毛细血管的发生。ZNF408与KIF11是近5年来新发现的与FEVR有关的致病基因，其中ZNF408编码在视网膜血管生成中发挥重要作用的转录因子，KIF11在眼发育和维持视网膜形态、功能方面发挥作用。

Familial exudative vitreoretinopathy （FEVR） is a hereditary disease with high geneticheterogeneity, including autosomal dominant inheritance, autosomal recessive inheritance, snd X-linked recessive inheritance. So far, six genes have been found to be associated with FEVR： Wnt receptor fizzled protein （FZD4）, Norrie disease （NDP）, co-receptor low-densitylipoprotein receptor-related protein 5 （LRP5）, and tetrasin 12 （TSPANI2）, zinc finger protein408 （ZNF408）, kinesin family member 11 （KIF11） gene. Among them, FZD4, NDP, LRPS, TSPANI2 and other four genes play an important role in the Norrin/Frizzled 4 signaling pathway. In retinal capillary endothelial cells, Norrin specifically controls the occurrence of ocular capillaries by activating the Norrin/Frizzled 4 signaling pathway. ZNF408 and KIF11 are newly discovered pathogenic genes related to FEVR in the past 5 years. ZNF408 encodes the transcription factor that plays an important role in retinal angiogenesis. KIF11 plays a role in eye development and maintenance of retinal morphology and function.