CANDIDATE GENE STUDY OF INHERITED RETINAL DEGENERATIONS

在这项资助下开始研究的3.5年里， 项目实验室已经成功地使用了候选基因 一种鉴定五种不同基因致病突变的方法 引起各种形式的视网膜色素变性(RP)和其他人类 光感受器疾病。项目实验室是第一个报告 五个基因鉴定中的四个。尽管取得了这些成功，但远远超过了 三分之二的RP病例仍有不明原因。基于 根据项目实验室和其他实验室的调查结果，似乎 RP及其亲缘关系患者的非等位基因和等位基因异质性 疾病是巨大的，可能100种中的任何一种都有各种突变。 能够引起临床相关疾病的不同基因座，包括 失明。项目实验室有一个由计算机管理的数据库 收集了数千名患有各种疾病的患者的DNA 光感受器退化和功能障碍。申请者将提高 这个集合的表型多样性通过登记其他 遗传性视网膜变性和功能障碍的患者。这个 申请者建议继续选择具有 在光感受器或其他视网膜的生理学中起重要作用 细胞，并分析这些基因在慢性病患者中的潜在突变 光感受器退化或功能障碍。他们将简化申请 突变筛查技术以增加无关基因的数量 选择每个候选基因进行调查的病例。如果成功，这将是 研究应确定导致遗传性心脏病形式的其他基因 致盲，如反光。

In the 3.5 years since research began under the auspices of this grant, the project laboratory has been successful in using the candidate gene approach to identify pathogenic mutations in five different genes that cause various forms of retinitis pigmentosa (RP) and other human photoreceptor diseases. The project laboratory was the first to report four of the five gene identifications. Despite these successes, well over two-thirds of cases of RP still have an unknown cause. Based on the findings of the project laboratory and other laboratories, it appears that the nonallelic and allelic heterogeneity among patients with RP and allied diseases is enormous, with various mutations at any of perhaps 100 different loci being able to cause clinically relevant disease, including blindness. The project laboratory has a computer-database managed collection of DNA from thousands of patients with a variety of photoreceptor degenerations and dysfunctions. The applicants will enhance the phenotypic diversity of this collection by enrolling additional patients with hereditary retinal degenerations and dysfunctions. The applicants propose to continue to select candidate genes having an important role in the physiology of the photoreceptors or other retinal cells, and to analyze those genes for potential mutations in patients with photoreceptor degeneration or dysfunction. They will apply streamlined techniques for mutation screening to increase the number of unrelated cases surveyed with each selected candidate gene. If successful, this research should identify additional genes causing forms of hereditary blindness such as RP.