基因突变是致盲眼病先天性白内障的主要病因，而对先白婴幼儿行眼部手术治疗尚存局限性，突变基因及致病功能研究，可望在先白非手术治疗上有所突破。现已定位明确的先白候选基因超过50个，但高通量测序仅覆盖60%，尚有大量未知基因及致病机制亟待揭示。项目申请人前期在一个常染色体显性先天性后极性伴皮质混浊家系中，鉴定了新致病基因蛋白质精氨酸甲基转移酶3（PRMT3）的突变，发现该基因点突变可能是该家系白内障发生成因。本项目拟进一步揭示PRMT3突变靶向p53/caspase-3介导的晶状体异常细胞增殖和先白发生的相关性，论证PRMT3点突变与先白形成的全新发病机制。并探索PRMT3突变表型拯救效应、筛选晶状体内PRMT3调控的其他可能靶点。初步阐明PRMT3点突变致先白发病的生命现象本质，可望尽早在先白发生、发展过程中加以非手术干预。为后续转化为对先白患者基因诊断和防治等非手术治疗提供新思路和理论依据。

Gene mutation is the leading cause of congenital cataract which can cause blindness. However, there are still limitations in eye surgery for infants. The research of mutant gene and pathogenic function is expected to make a breakthrough in non-surgical treatment of congenital cataract. To date, more than 50 candidate genes of congenital cataract have been identified, however, high-throughput sequencing only covers 60% of them and a large number of unknown genes and pathogenesis remains to be revealed. The applicant identified a novel pathogenic gene, protein-arginine methyltransferases 3 (PRMT3) in an autosomal dominant congenital cataract pedigree with cortical and posterior polar opacity, and found that the heterozygous mutation of PRMT3 might be the cause of cataract in this pedigree. This project aims to further elucidated the correlation between PRMT3 mutation targeting p53/caspase-3 mediated abnormal lens cell proliferation and congenital cataract development, and demonstrate a brand-new pathogenesis of PRMT3 mutation and congenital cataract. Moreover, the project intends to explore the phenotypic rescue effect as well as screen other potential targets and signaling pathways regulated by PRMT3 in the lens. The obtained results will help to preliminary clarify the nature of life phenomena of congenital cataract induced by PRMT3 mutation, further providing insights into non-surgical intervention in the occurrence, development and prognosis of the disease. It can provide innovative ideas and theoretical basis for the transformation into non-surgical treatment schemes including gene diagnosis, prevention and treatment of congenital cataract.