CANDIDATE GENE STUDY OF INHERITED RETINAL DEGENERATIONS

在这项资助下开始研究的3.5年里， 该项目实验室已经成功地利用候选基因 一种方法来识别五种不同基因中的致病突变， 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 五个基因中的四个尽管取得了这些成功， 三分之二的RP病例仍有未知原因。基于 根据项目实验室和其他实验室的调查结果， RP及其同源基因的非等位基因和等位基因异质性 疾病是巨大的，在任何一个可能的100个突变， 不同的基因座能够引起临床相关疾病，包括 失明该项目实验室有一个计算机数据库管理 从数千名患有各种疾病的患者中收集DNA， 光感受器退化和功能障碍。申请人将提高 该集合的表型多样性通过招募额外的 遗传性视网膜变性和功能障碍患者。的 申请人提出继续选择具有以下特征的候选基因： 在光感受器或其他视网膜的生理学中的重要作用 细胞，并分析这些基因的潜在突变患者 光感受器变性或功能障碍。他们将采用精简的 突变筛查技术，以增加不相关的 用每个选定的候选基因调查病例。如果成功，这 研究应确定其他基因引起的遗传形式， 像RP这样的失明。

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.