常染色体显性遗传性视网膜色素变性家系致病基因的定位研究  

Preliminary mapping of an autosomal dominant retinitis pigmentosa gene by linkage analysis

作　　者：丁锋[1] 周新[2] 袁媛[2] 严明[3] 郑芳[2] 

机构地区：[1]华中科技大学同济医学院附属普爱医院检验科,武汉430033 [2]武汉大学中南医院基因诊断中心 [3]武汉大学中南医院眼科

出　　处：《中华医学遗传学杂志》2011年第6期634-637,共4页Chinese Journal of Medical Genetics

基　　金：基金项目：国家自然科学基金（30672012）

摘　　要：目的对1个常染色体显性遗传的视网膜色素变性家系进行致病基因定位，并对候选基因进行突变筛查。方法收集1个视网膜色素变性家系，对其成员进行系统的眼科检查。抽取家系成员外周血并提取DNA，用连锁分析方法定位家系的致病基因，对定位区域的候选基因进行突变筛查。结果两点连锁分析结果在微卫星标记DIS252处获得最大两点LOD值2．02（0—0．00时），多点连锁分析结果显示LOD值在DIS252处具有最大LOD值2．28。但直接测序在该区域的两个候选基因中均未发现突变。结论该家系致病基因定位于lp21．1-q23．3之间。两个候选基因PRPF3与SEMA4A可能并非该家系的致病基因，附近可能存在1个未知的致病基因。Objective To map the gene responsible for a three generations family with autosomal dominant retinitis pigmentosa （ADRP） and screen the mutation in candidate genes. Methods For a 14- member family with 7 suspected patients, systematic and ophthalmic examinations were performed including visual acuity, ophthalmoscopy, perimetry and electrophysiologic test. After the genomic DNA was extracted, genome scanning was performed, and candidate genes were screened for potential mutations. Results The maximal two-point LOD score was obtained at D1S252 with a value of 2.02 （0= 0.00）, and multi-point LOD score reached its maximum 2.28 at D1S252. However, no mutations were detected in two candidate genes in this region, namely PRPF3 and SEMA4A by direct sequencing. Conclusion Significant evidence for linkage was found at the chromosome region of lp21.1-q23.3. However, neither PRPF3 nor SEMA4A has harbored a mutation. There may exist an additional gene which is responsible for this disease.

关 键 词：视网膜色素变性 连锁分析 微卫星标记 

分 类 号：R774.1[医药卫生—眼科]