常染色体显性视网膜色素变性家系基因定位的研究与视紫红质基因突变的检测分析  

Localization of autosomal dominant retinitis pigmentosa gene and the mutation of rhodopsin gene

作　　者：马晓晔[1] 魏锐利[1] 蔡季平[1] 朱莉[1] 

机构地区：[1]第二军医大学附属长征医院眼科,200003

出　　处：《中国实用眼科杂志》2002年第7期497-499,I001,共4页Chinese Journal of Practical Ophthalmology

基　　金：国家自然科学基金资助项目 (39770 785) ;国家人类基因组南方研究中心的大力协助。

摘　　要：对一常染色体显性视网膜色素变性 (autosomaldominantretinitispigmentosa ,ADRP)大家系进行基因定位 ,并检测该家系12名患者的视紫红质基因是否存在突变。方法 :采用多个已知位点的遗传标记对该ADRP家系进行连锁分析 ,确定致病基因的大致染色体位置 ;在所定位的染色体区域将RHO基因作为侯选基因进行直接测序检测突变。结果 :连锁分析结果发现遗传标记D3S12 92 ,当θ =0 1时有最大Lod值 =2 732 85 2 ,因此考虑该家系致病基因位于D3S12 92附近。直接测序结果发现该家系中大部分患者在RHO基因的第 3外显子序列 ,第 182密码子的第 2个碱基发生G→A置换突变 ,导致甘氨酸 (Gly)变为天冬氨酸 (Asp) ,命名为Gly -182 -Asp突变 ,而在 2例患者中则未发现突变 ;同时 ,在该家系正常成员以及正常对照者中均未发现此突变。结论 :ADRP存在分子水平的遗传异质性 ,某些ADRP是由于RHO基因突变所致。但是由于本研究所涉及的ADRP家系中尚有2名患者未找到RHO基因突变 ,故不能将Gly -182 -Asp突变认为是该家系的致病原因。在D3S12 92与RHO基因之间可能存在新的基因 ,还需进一步研究证明。Objective:To localize the gene of autosomal dominant retinitis pigmentosa (ADRP) with a hereditary family of 12 ADRP patients,and to investigate the mutation of rhodopsin gene Methods:Two-point linkage analysis with microsatellite markers was performed.The mutation screening of rhodopsin gene was carried out with direct genomic sequencing. Results:Linkage analysis showed that the maximum LOD score reaching 2 732852 at marker D3S1292 at recombination fraction θ=0.1.The outcome of direct genomic sequencing showed a guanine to adenine transition mutation in codon 182 in exon 3 of the rhodopsin gene that resulted in a glycine to aspartic change (Gly-182-Asp) in 10 patients,but not in the rest members of the family. Conclusions:It is suggested that molecular genetic heterogeneity exists in ADRP,and that some subtypes of ADRP might be caused by point mutations of the rhodopsin gene.Since there are two affected members on whom the mutation could not be detected,the Gly-182-Asp mutation in the rhodopsin gene cannot be confirmed as the disease causing of the family.There might be other gene that is responsible for the disease between the rhodopsin gene and the marker D3S1292.

关 键 词：常染色体显性视网膜色素变性 基因定位 视网膜色素变性 常染色体显性 基因突变 视紫红质 ADRP 

分 类 号：R774.13[医药卫生—眼科]