眼相关罕见病的临床诊疗模式及分子发病机制研究

眼相关罕见病（Ocular　Rare　Diseases， ORD）约400余种，80%以上属于遗传病，相关致病基因近千种，发病机制复杂多样；可累及眼的各个组织以及全身其他器官，常导致不可逆盲或严重视功能障碍。本课题针对我国ORD知晓度低及临床诊断准确率低的现状，基于申请者团队多年相关临床及基础研究的成果，拟对ORD进行规范临床信息采集，探索临床诊疗关键点及模式；对ORD进行基因检测及分子诊断，并用全外显子及全基因组测序技术，发现新的致病基因；构建患者来源iPSCs作为细胞模型研究分子发病机制。基于本研究获得资料及数据可以得到自主知识产权的成果：1）归纳出代表性ORD临床诊疗模式，从而提高诊疗准确率；2）确定高性价比及高精准度ORD基因检测方案；3）获得ORD分子病理通路。本研究成果能够作为ORD诊疗新策略的理论依据, 并且推动ORD医药研发的深入。

Ocular Rare Diseases (ORD) consist of 400 subtypes, more than 80% of which are inherited associated with near 1000 genes. The underlying pathogenesis is multifarious and complicated. ORD may involve ocular tissues and be symdromic, leading to irreversible blindness or severe visual impairment. Currently, the public awareness of ORD is poor and misdiagnosis of ORD is high in our country. Based on our previous clinical and basic research experiences and accomplishments, this proposed project will focus on ORD by clinical framework and registry study; multi-modality gene research including whole exome/genome sequencing to indentify novel disease genes; constructing patient-derived iPSCs to explore the molecular pathogenesis. The output of this project contains: 1) establish preferred practice pattern of ORD, which will improve the standard of patient care; 2) provide cost-effective gene testing strategy for ORD with high accuracy; 3) elucidate ORD molecular pathological pathway. The achievement of this project will push forward the development of innovative medical and pharmaceutical technology for ORD.