视网膜色素变性(RP)是一类常见且危害最严重的遗传性致盲眼病，具临床表现复杂，遗传异质性高和致病基因众多等特征，使其临床基因诊断颇具挑战性。另外，尚有相当数量的未知RP致病基因亟待挖掘。本课题拟在前期基础上扩容RP遗传资源专题数据库，应用基于DNA池的PCR-HRM分析技术，建立高性价比和高通量的RP致病基因突变筛查技术平台，大量筛查和鉴定RP致病基因突变，构建我国RP致病基因图谱及其突变频谱。对于排除已知致病基因的RP家系，则应用全基因组SNP扫描、连锁分析和目标序列捕获的二代测序或外显子组测序等技术发现新致病基因，分析其生物学功能，阐明其致病的分子机制。项目的顺利实施和完成可望实现RP临床分子诊断，为该类疾病的基因治疗、预防与干预决策制定提供科学依据；RP新致病基因的发现亦将进一步丰富和拓展人类对RP的认知。

Retinitis pigmentosa (RP) is the most common and severe hereditary ocular disease, leading to severe visual impairments or even blindness. RP presents significant and complex clinical and genetic heterogeneities involvinging massive disease-causing genes. Therefore, it has been a great challenge for molecular diagnosis of RP. In addition, a large number of unknown RP-causing genes are yet to be discovered. In this project, we will continue to collect blood samples and clinical data of RP disease to expand the RP genetic resources database based on our previous work. We will develop a high throughput and cost-effective massive mutation screening technical platform for detecting RP-causing genes based on PCR-HRM (High-resolution melting) analysis with DNA pooling as PCR templates. And then we will identify the causative mutations of known RP-causing genes in a larger number of patients with RP disease, and construct the distribution of genes and their mutation spectra in Chinese population of RP patients. Later, we will discover some new disease-causing genes using the genome-wide SNP scans, linkage analysis and targeted next-generation sequencing or exome sequencing technology in the RP families, which have been excluded the known RP genes. Furthermore, we will study on the biological function of the new RP-causing genes for illuminating their pathogenic mechanisms. In conclusion, if the project has been implemented and completed successfully, we will achieve clinical molecular genetics diagnosis for RP, and offer the scientific strategies for gene therapy, prevention and intervention of the RP disease. The discovery of the new RP-causing genes will further enrich and expand our understanding the RP disease.