先天性白内障大家系致病基因的定位克隆与功能研究

项目名称： 先天性白内障大家系致病基因的定位克隆与功能研究

项目编号： No.81200722

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 张璐

作者单位： 哈尔滨医科大学

项目金额： 23万元

中文摘要： 先天性白内障是儿童主要致盲眼病之一，主要由于遗传因素所致，有临床和遗传异质性。本课题着眼于先天性白内障的发病机制研究，收集迄今为止人数最大的先天性Coppock白内障大家系，从基因扫描入手筛选先天性白内障的致病基因，对候选致病基因进行突变检测，发现GJA3基因的143位突变是潜在的致病原因。为了进一步确认此突变的致病性，首先，分析突变与疾病发生的相关性，确实前期的基因扫描结果；其次，由于GJA3是细胞连接相关蛋白，以此为切入点，在分子，细胞水平对其野生型和突变型的功能进行考察，明确GJA3基因突变的致病机制；最后，通过建立基因突变鼠模型，确实GJA3基因突变是Coppock白内障致病原因。本研究旨在通过临床筛查- - 机制研究-动物模型核实，全面而可靠地研究先天性Coppock白内障的发病机制。研究结果将为先天性白内障的早期诊断、产前诊断和基因治疗提供科学依据。

中文关键词： 先天性白内障；GJA3 （Cx46）基因；基因突变；功能研究；

英文摘要： Congenital cataract is a significant cause of vision loss in infants. One quarter of congenital cataract is hereditary. It is a clinically and genetically heterogeneous lens disorder. This research focused on the pathogenesis of congenital cataract. We collected one so far the largest congenital Coppock cataract family. Gene scan and DNA sequencing were performed to localize and identify the susceptible gene. Direct sequencing of the candidate GJA3 gene revealed a G143R mutation. In order to confirm the pathogenesis of the mutation, first of all, analysis the correlation of gene mutation and congenital cataract, confirm the result of gene scan; Second, since GJA3 is gap-junction protein, based on this point, examine the function of wild type and mutation type in molecular and cellular level, investigate the pathogenic mechanism of GJA3 gene mutation; Finally, through establish the gene mutation rat model, confirm GJA3 gene mutation is the pathogenesis of congenital Coppock cataract. This research aims to through the clinical screening-mechanism research-animal model to verify the pathogenesis of congenital Coppock cataract. The results will provide scientific basis for early diagnosis, prenatal diagnosis and gene therapy of congenital cataract.

英文关键词： congenital cataract；GJA3 （Cx46）gene；gene mutation；function research；