常染色体显性视网膜色素变性家系基因定位  

Localization of genes in a family with autosomal dominant retinitis pigmentosa

作　　者：张宝全[1] 章雪敏[1] 刘铁城[1] 金鑫[1] 袁慧军[2] 

机构地区：[1]解放军总医院眼科,北京100853 [2]解放军总医院耳鼻咽喉头颈外科研究所,北京100853

出　　处：《解放军医学院学报》2013年第5期440-442,445,共4页Academic Journal of Chinese PLA Medical School

基　　金：军队"十一五"面上课题(2006wzbh26)~~

摘　　要：目的探讨一常染色体显性视网膜色素变性（autosomal dominant retinitis pigmentosa,adRP）家系致病基因与盘膜边缘蛋白/视网膜变性慢基因（eripherin/retinal degeneration slow,RDS）、视杆外节盘膜蛋白1基因（retinal outer segment membraneprotein 1,ROM1）、视锥杆细胞同源盒基因（cone-rod homeobox gene,CRX）、神经视网膜亮氨酸拉链基因（neural retinalleucine zipper,NRL）、鸟甘酸环化酶激活1B基因（guanylate cyclase activator 1B,GUCA1B）、肌动蛋白同源2基因（fascinhomolog 2,FSCN2）和拓扑异构酶结合1基因（topoisomerase I binding,TOPORS）多发突变位点的关系。方法采集一个连续4代发病的RP家系14个成员外周血4~5 ml,提取基因组DNA,采用聚合酶链反应（plymerase chain reaction,PCR）对常见的7个adRP候选基因的17个外显子多发突变位点进行扩增,PCR产物纯化后直接测序,测序结果与美国国立生物技术信息中心（National Center for Biotechnology Information,NCBI）数据库中公布的核酸标准序列进行比对分析。结果该家系视网膜色素变性为常染色体显性遗传,家系成员在RDS、ROM1、CRX、NRL、GUCA1B、FSCN2和TOPORS基因中未发现致病突变,仅在RDS基因第1外显子和第3外显子编码区发现5处单核苷酸改变。结论 RDS、ROM1、CRX、NRL、GUCA1B、FSCN2和TOPORS不是本研究家系的致病基因,RDS基因外显子中的5处单核苷酸的改变为单核苷酸多态性（single nucleotide polymorphism,SNP）。Objective To study the relation of pathogenic genes in a Chinese family with autosomal dominant retinitis pigmentosa（adRP） with eripherin/retinal degeneration slow（RDS）,retinal outer segment membrane protein 1（ROM1）,cone-rod homeobox-containing gene（CRX）,neural retinal leucine zipper（NRL）,guanylate cyclase activator 1B（GUCA1B）,fascin homolog 2（FSCN2） and topoisomerase I binding（TOPORS）.Methods Peripheral blood samples（4-5 ml） were taken from the 4 families with adRP.Genomic DNA was purified using an extraction kit.Seventeen exons of 7 adRP candidate genes were amplified by polymerase chain reaction（PCR）.The PCR products were directly sequenced after purified and compared with the standard sequences from the GenBank.Results The inherited mode of this family was adRP.In members of this family,no variation was found in the RDS,ROM1,CRX,NRL,GUCA1B,FSCN2 and TOPORS candidate genes,but 5 single nucleotide polymorphisms（SNP） were detected in exons 1 and 3 of RDS gene.Conclusion RDS,ROM1,CRX,NRL,GUCA1B,FSCN2 and TOPORS candidate genes are not the pathogenic genes in this family.The 5 SNP exons of RDS are SNP.

关 键 词：视网膜色素变性 常染色体显性 候选基因 单核苷酸多态性 

分 类 号：R774.1[医药卫生—眼科]