视网膜色素变性患者中视网膜色素变性1基因点突变的研究  

Mutation analysis of retinitis pigmentosa 1 gene in Chinese with retinitis pigmentosa

作　　者：张晓莉[1] 杨冠寅[2] 彭智培[2] 府伟灵[1] 

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：《中华医学遗传学杂志》2002年第3期194-197,共4页Chinese Journal of Medical Genetics

摘　　要：目的　研究中国视网膜色素变性 (retinitis pigmentosa,RP)患者 RP1基因的突变频率、特征及其在 RP发病机理中所起的作用。方法　运用构象敏感凝胶电泳 (conformation sensitive gelelectrophoresis,CSGE)和 DNA直接测序方法对 10 1例香港地区 RP患者的 RP1基因全编码区进行突变的筛选与检测。结果　 10 1例 RP患者中检出 1例患者携带常见的 RP1致病突变 - R6 77X,另外在 3名正常个体及 1例 Stargardt患者中检出非致病的无义突变 - R1933X。 RP1基因在所有 RP患者中的突变检出率为 1/10 1。突变最终导致 RP1蛋白严重截短。此外 ,在本研究人群中还发现 10个错义突变 ,除 M479I的病理意义未确定之外 ,其余均系 RP1基因的多态现象。结论　 R1933X无致病意义 ,提示羧基端 2 2 4个氨基酸的区域可能为 RP1蛋白非功能区 ,结合最近发现的 RP1羧基端的移码突变 - Y10 5 3(1bp del)的病理意义 ,推测 RP1蛋白中相应片段 (密码子 10 5 2～ 1933)的缺失会导致 RP的发生。为证实这种推测 ,大范围的 RP1基因分型工作是有必要的 ,并且可同时发现更多的 RP致病突变以及不同于其他种族人群的 RP1基因多态变化。Objective: To investigate the frequency and pattern of RP1 point mutations in Chinese retinitis pigmentosa (RP) patients and to examine their effects on the development of RP. Methods: Conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing were used to determine sequence alterations occurring in the entire coding region of the RP1 gene in 101 Chinese RP patients in Hong Kong. Results: R677X was detected in one RP patient. A nonpathogenic nonsense mutation, R1933X, was identified in three normal individuals and one patient. with Stargardt disease. The frequency of RP1 mutations among all RP patients in this study is 1/101. R677X is expected to lead to large disruptions of the encoded protein. Additionally, 10 more missense alterations in the RP1 gene were identified in the subjects of this study . Apart from M479I whose pathogenicity can not be determined currently, other sequence changes are just polymorphisms of the RP1 gene. Conclusion: The nonpathogenicity of R1933X indicates that the C-terminal 224 residues of RP1 protein may be not critical for RP1. Recently, a C-terminal truncating mutation, Y1053(1 bp del), was reported to occur in an RP patient. Thus RP can be caused by lack of the region of RP1 protein after codon 1052 but before 1933. To confirm such a proposition, a large genotyping study is necessary and is likely to reveal more RP causative mutations and uncover more sequence alterations different from those of other ethnic groups.

关 键 词：视网膜色素变性 基因点突变 研究 构象敏感凝胶电泳 DNA测序 

分 类 号：R774.1[医药卫生—眼科]