引起两个中国家系产生X连锁视网膜色素变性的RPGR基因的两个新突变

摘要

目的检测引起两个中国家系产生X连锁视网膜色素变性的RPGR基因突变.方法以人类基因组DNA为模板,用位于内含子内的引物扩增出RPGR基因外显子1-19 的PCR片段.PCR产物经SSCP分析后直接进行测序.通过比较病人和正常人相应的DNA顺序,检出基因突变位点.结果在两个家系检测到两个新突变c1536delC和E332X,它们分别位于RPGR基因的第12和第9外显子(这是两个外显子首次发现的突变).两突变均可导致翻译提前终止,产生不具备正常功能的截短蛋白.结论两个突变是相应家系产生视网膜色素变性的遗传学基础,所得结果有助于分析RPGR蛋白功能.%Objective To detect mutations of the retinitis pigmentosa GTPase regulator (RPGR) gene in two Chinese X-linked retinitis pigmentosa families. Methods Fragments of exons 1-19 of the RPGR gene were amplified with intronic primers, using genomic DNA as template. The polymerase chain reaction (PCR) products were analysed by single-strand conformation polymorphism (SSCP) and direct sequencing. Mutations were identified by comparing DNA sequences of the patients with those of the normal controls.Results Two novel mutations, c1536delC and E332X, were identified in exons 12 and 9 of the RPGR gene in both families. Each mutation was the first mutation found in their respective exons. Both mutations were predicted to cause premature termination, which resulted in truncated proteins without normal functions of the RPGR products.Conclusions Both mutations are the genetic basis of the pathogenesis in the respective families. Our data might be helpful in analysing the function of the RPGR protein.