视网膜色素变性患者视紫红质E341ter基因突变及临床表型分析  

A novel rhodopsin E341ter mutation in patients with retinitis pigmentosa and corresponding clinical phenotype

作　　者：熊世红[1] 赵堪兴[1] 王立[1] 王乐今[1] 崔云[1] 陈薇樱[1] 王黎明[1] 王擎 

机构地区：[1]天津市眼科医院,天津市眼科研究所 [2]Center for Molecular Genetics,Cleveland Clinic Foundation

出　　处：《中华眼科杂志》2002年第4期224-227,T004,共5页Chinese Journal of Ophthalmology

基　　金：国家自然科学基金杰出青年科学基金资助项目(3 982 5 5 10 )

摘　　要：目的　探讨常染色体显性遗传视网膜色素变性患者视紫红质基因突变及其与临床表型的关系。方法　应用聚合酶链反应 (polymerasechainreaction ,PCR)和单链构象多态性 (singlestrandconformationpolymorphism ,SSCP)技术 ,对 13个常染色体显性遗传视网膜色素变性家系中的 2 7例成员 ,进行视紫红质基因整个编码区的突变筛选 ,对SSCP检测有变异带的外显子PCR产物进行测序 ;同时应用裂隙灯、眼底镜、动静态视野计和视网膜电流图 (ERG)对患者进行临床检测。随机收集 30例正常人进行对照检测。结果　发现 1个家系患者有视紫红质E34lter突变 ,呈杂合子 ,密码子 341第一个碱基由G变成T。该家系临床表现为青年期出现夜盲 ,视力和视野损害较重 ,ERG检查杆体和锥体无反应或仅有较小的锥体反应。结论　视紫红质基因突变家系的视网膜色素变性病史开始于杆体功能的丢失 ,进而累及锥体系统 ,并最终导致视功能严重丧失。Objective To detect rhodopsin (RHO) mutation in Chinese families with autosomal dominant retinitis pigmentosa (ADRP) and study on the association of RHO gene mutations with clinical phenotype Methods Twenty seven members from 13 Chinese families with ADRP and 30 normal subjects were recruited The complete coding regions of the rhodopsin gene were amplified with polymerase chain reaction (PCR) and then DNA single strand conformation polymorphism (SSCP) technique was used to screen RHO gene mutations When a variant band was observed after the SSCP electrophoresis, the variant band was analyzed by sequencing PCR amplified DNA All subjects were examined clinically by slit lamp, direct funduscopy, Goldmann kinetic perimetry, Humphery threshold perimetry and eletroretinogram Results Nine affected subjects and 2 boys (11 and 9 years old respectively) in one pedigree among 13 families were found to have three DNA single strand bands by SSCP analysis Results of assaying sequence showed the 11 members were heterozygous for rhodopsin E341ter mutation The codon 341 is changed from GAG to TAG, resulting in a stop codon mutation Thirty normal controls and unaffected subjects in this family were the wild type of RHO gene Affected individuals reported night blindness in the second decade, showed optic atrophy, vessel attenuation and a few bone spicule like pigments in the peripheral retina The impairment of visual acuity was relatively severe, loss of peripheral visual field was greatly considerable after 30 years of age, rod and cone ERG were not detectable in the second decade, and only slight cone response was left Conclusions The natural history of RP in this family begins with a loss of rod function, progresses to involve the cone system, and leads eventually to a severe loss of visual function A novel rhodopsin gene mutation E341ter is responsible for a Chinese family with ADRP

关 键 词：视网膜色素层变性 视紫质 基因突变 E341ter 临床表型 

分 类 号：R774.1[医药卫生—眼科]