先天性无虹膜致病基因的鉴定与功能研究

Aniridia is a panocular genetic disorder characterized by a variable degree of iris hypoplasia as well as several other ocular features including dystrophy, cataract and glaucoma. It extremely affects patient's quality of life and could not be effectively cured so far. This study is to screen gene mutations by enlarging AN samples in PRR5L gene which has been identified in our previous study. mRNA expression and localization of this gene in human tissue are determined by RT-PCR, in situ hybridization and immunohistochemistry, respectively. Cell biology research will be performed to explore the effect of this mutation on PRR5L gene in vitro. The pathogenic mechanism of AN will be investigated by zebrafish, transgenic mice and knockout mice model in vivo; The purpose of this study is to examine the function of PRR5L gene in AN and reveal the role of this gene in causing AN, and to clarify the pathophysiological mechanisms of AN, which could provide new approaches and targets for clinical treatment and have important theoretical significance and potential clinical applications.

先天性无虹膜（Aniridia，AN）是一种严重的眼科遗传疾病，其特征为全部或部分虹膜缺失或发育不良，伴白内障、青光眼等病变，极度影响患者的生活质量，迄今无法有效根治。本研究拟在前期发现的一个新的AN致病基因-PRR5L基础上，扩大样本鉴定该基因在AN病人中的突变情况；通过RT-PCR、原位杂交、免疫组化等方法检测其表达情况；体外细胞生物学研究突变体对该基因功能的影响；并通过斑马鱼、转基因和基因敲除小鼠模型体内研究其致病机制。本研究旨在明确PRR5L的基因功能及其在先天性无虹膜发生发展过程的作用，能够更好的阐明AN的病理生理机制并为临床治疗提供新的途径和靶点，具有重要的理论意义和潜在的临床应用价值。

先天性无虹膜（Aniridia，AN）是一种严重的眼科遗传疾病，其特征为全部或部分虹膜缺失或发育不良，伴白内障、青光眼等病变，极度影响患者的生活质量，迄今无法有效根治。本研究拟在前期发现的疑似AN致病基因PAX6、LMO2基础上，扩大样本鉴定该基因在AN病人中的突变情况；通过RT-PCR、原位杂交、免疫组化等方法检测LMO2表达情况；体外细胞生物学研究LMO2突变体对该基因功能的影响；并通过制作了LMO2基因敲除和敲入小鼠模型研究LMO2与AN致病机制。并在一个家系中研究新发现了一个PAX6基因3‘下游存在一470k的缺失，本研究明确PAX6基因3·区域和 LMO2基因在先天性无虹膜发生发展过程的作用，更好的阐明AN的病理生理机制，具有重要的理论意义和潜在的临床应用价值。