一个常染色体显性遗传视网膜色素变性家系突变基因筛查

Screening for the in a Autosomal Dominant Pathogenic Mutations Retinitis Pigmentosa Pedigree

目的对一个四代常染色体显性遗传视网膜色素变性家系进行突变基因的筛查。方法选取了常见的11个视网膜色素变性（retinitis pigmentosa，RP）相关致病基因：视紫红质（rhodopsin，RHO，RP4）基因、视网膜变性慢蛋白（peripherin 2／retinal degeneration slow PRPH2／RDS，RP7）基因、视网膜色素变性1（retinitis pigmentosa 1，RP1）基因、前体mRNA处理因子31（pre—mRNA processing factor31，PRPF31，RP11）基因、次黄苷单磷酸脱氢酶1型（inosine monophosphate dehydrogenase 1，IMPDH1，RP10）基因、视杆外节蛋白1（rod outer segment protein 1，ROM1）基因、神经视网膜亮氨酸拉链（neural retina leucine zipper，NRL，RP27）基因、Pim1激酶相关蛋白1（piml—kinase associated protein1，PAP1，RP9）基因、视锥-视杆同源盒（cone—rod homeobox—containing，CRX）基因、前体mRNA处理因子3（pre—mRNA processing factor3，PRPF3，RP18）基因、前体mRNA处理因子8（pre—mRNA processing factor 8，PRPF8，RP13）基因。通过聚合酶链式反应扩增这11个RP相关致病基因的外显子和邻近拼接位点，扩增产物进行正、反双向测序。结果①对常见的11个RP相关致病基因的64个片段的研究显示，除了基因多态性和内含子的变异外，未发现与疾病有关的外显子或邻近拼接住点的突变。②首次在中国人种中发现RP9基因的c．629A→G，（Lys210Arg）变异。结论该文设计研究的突变基因未被检测到，表明此家系在11个RP相关致病基因的外显子和邻近拼接位点无基因突变。

Objective To screen for the pathogenic mutations in a four-generation autosomal dominant retinitis pigmentosa （ADRP） pedigree. Methods The exons and splicing sites of 11 RP related genes （Rhodopsin,RHO,RP4;peripherin 2/ retinal degeneration slow PRPH2/RDS ,RP7 ;retinitis pigmentosa 1 ,RP1 ;pre-mRNA processing factor 31 ,PRPF31 ,RPll ; inosine monophosphate dehydrogenase 1 ,IMPDH1 ,RP10;rod outer segment protein 1 ,ROM1 ;neural retina leucine zipper, NRL, RP27 ; piml-kinase associated protein 1, PAP1, RP9 ; cone-rod homeobox-containing, CRX ; pre-mRNA processing factor 3, PRPF3, RP18 and pre-mRNA processing factor 8, PRPF8, RP13） were amplified by polymerase chain reaction （PCR）. The PCR products were bi-directionally sequenced to screening for mutations. Results In the 64 fragments amplified ,no pathogenic mutations were found except previously reported polymorphisms and mutations of the intron region,although they found for the first time in the Chinese population c. 629A→G, （Lys210Arg） mutation in the RP9 gene. Conclusion Did not detect mutations in the loci that we screened,which suggests that the pedigree has no mutations in exons and splicing sites of the 11 RP related genes.