视网膜色素变性光感受器发育相关基因分型的研究

目的 探讨一新近发现的与氧调节光感受器发育相关基因(0RPl)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0RPl基因全编码区进行突变的筛选与检测。结果 检出一0RPl致病突变因子R677X，并首次发现一非致病的无义突变出子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0RPl基因突变所致。R1933X无致病意义，结合最近发现的Y1053(1—bPdel)的病理意义，推测密码子1052至1933区域的稳定对0RPl结构及功能的维持起着重要的作用。

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

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.