视网膜色素变性光感受器发育相关基因分型的研究  

Role of mutations in a novel photoreceptor-specific gene in the pathogenesis of retinitis pigmentosa

作　　者：张晓莉[1] 府伟灵[1] 彭智培[2] 杨冠寅[2] 

机构地区：[1]第三军医大学西南医院基因诊断治疗中心,重庆400038 [2]香港中文大学眼科及视觉科学系

出　　处：《眼科研究》2003年第1期21-23,共3页Chinese Ophthalmic Research

摘　　要：目的 探讨一新近发现的与氧调节光感受器发育相关基因(0RP1)在常染色体显性遗传(RP)发病机制中的作用。方法 运用聚合酶链反应(PCR)、构象敏感凝胶电泳(CSGE)和DNA直接测序方法对92例RP患者ORP1基因全编码区进行突变的筛选与检测。 结果 检出-ORP1致病突变因子R677X,并首次发现一非致病的无义突变因子R1933X。 结论 预测香港地区大约有1.1％(95％的可信区间为5.4％以下)的RP是由ORP1基因突变所致。R1933X无致病意义.结合最近发现的Y1 053(1-bp del)的病理意义,推测密码子1052至1 933区域的稳定对ORP1结构及功能的维持起着重要的作用。Objective To examine the role of oxygen-regulated photoreceptor protein 1 ( ORP1 ) mutations in pathogenesis of retinitis pigmentosa of Chinese RP patients. Methods Leukocyte DNA was isolated from the blood of 92 unrelated HK patients diagnosed with RP and 100 subjects without known eye disease. The conformation sensitive gel electrophoresis technique and direct sequencing were used to evaluate 26 DNA fragments amplified from the DNA samples, that in total encompassed the entire coding region. Results Totally, 2 nonsense mutations and 8 missense alterations in the ORP1 gene were identified in the subjects investigated, among which 4 are novel. Arg677X,the most common found in Americans, was detected in 1 RP patient. A non-disease causing polymorphism,Arg 1933X,was identified in I control subject and 3 members of a non-RP family. Arg677X was expected to lead to large disruptions of the encoded protein. Conclusions RP1 mutations cause about 1. 1% (95% conlidence interval: 0. 0% -5.4% ) of all RP in Chinese. The C-terminal 224 residues of ORP1 protein may not be critical for ORP1 function. The most C-terminal truncation previously reported was due to Tyrl053(1-bp del)and delected in RP patients. Thus at least part of the ORP1 protein after amino acids 1052 but before 1933 must be present at undiminished levels in order to maintain healthy photoreceptor function.

关 键 词：氧调节 光感受器 发育 基因 0RPl PCR 聚合酶 链反应 DNA 视网膜色素变性 基因突变 构象敏感凝胶电泳 

分 类 号：R774.1[医药卫生—眼科]