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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 characteristics of RP1 gene mutation in Chinese patients with retinitis pigmentosa (RP) and its role in the pathogenesis of RP. Methods The full-length RP1 gene of 10 patients with RP in Hong Kong was screened and detected by conformation-sensitive gelelectrophoresis (CSGE) and DNA direct sequencing. Results One out of 101 patients with RP was found to carry the common RP1 pathogenic mutation R677X. In addition, a nonpathogenic nonsense mutation R1933X was detected in 3 normal individuals and one Stargardt patient. The mutation rate of RP1 gene in all RP patients was 1/10 1. Mutations ultimately result in a severely truncated RP1 protein. In addition, 10 missense mutations were also found in this study population, with the exception of the pathological significance of M479I was undetermined, the rest were all polymorphisms of the RP1 gene. Conclusion R1933X has no pathological significance, suggesting that the region of 22 4 amino acids at the carboxy terminus may be the non-functional region of RP1 protein. Combined with the recently discovered pathogenic significance of the frame-shifting mutation at the carboxyl terminus of RP1, Y10 5 3 (1bp del) The deletion of the corresponding fragment (codon 1052-1933) leads to the occurrence of RP. To confirm this speculation, a wide range of RP1 genotyping efforts are necessary and more RP-related mutations and different polymorphisms in the RP1 gene may be found simultaneously with other ethnic groups.