橄榄-桥脑-小脑萎缩伴视网膜变性的临床及分子生物学研究  

Clinical and molecular biological study on olivopontocerebellar atrophy with retinal degeneration

作　　者：顾卫红[1] 王国相[1] 王燕琪[2] 刘兴洲[1] 周宝玉[1] 杜浩萍 王晓工[1] 李爱红[2] 

机构地区：[1]中日友好医院神经内科,100029 [2]中日友好医院眼科,100029

出　　处：《中华神经科杂志》2000年第2期93-97,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金!39470263

摘　　要：目的探讨橄榄－桥脑－小脑萎缩伴有视网膜变性（SCA7）的临床表型与致病基因突变的关系。方法对发病表现为共济失调、辨色力异常、视力下降的2个家系共21名成员（8例患者）进行了系统的临床及辅助检查，通过聚合酶链反应（PCR）及聚丙烯酰胺凝胶电泳等技术检测家系成员和另55名健康人的SCA基因内CAG重复序列，分析SCA7临床表型与CAG重复突变的相关性。结果2个家系11个系代-子代对均存在遗传早现现象，在父系遗传时更为明显。正常等位基因CAG重复数目为9～18，8例患者的异常等位基因的CAG重复数目为44～85，两者之间存在非常显著的差异。1例无临床症状病例的异常等位基因CAG重复数目为59。异常扩展的CAG序列呈现代间不稳定性，重复数目与发病年龄呈明显负相关关系（r＝－0．883，P＝0．005），并与症状严重程度有关，这一特点在父系遗传时更为明显。初步发现突变等位基因的CAG重复序列在外周血白细胞中存在镶嵌现象。结论从临床及基因学方面确认国人SCA7家系的存在，阐明其临床特征，建立国人SCA7基因学诊断标准；致病基因内CAG重复数目呈代间不稳定且与发病年龄呈负相关，此为遗传早现的分子基础。Objectives To investigate the relationship between the clinical features and the gene mutation of olivopontocerebellar atrophy with retinal degeneration. Methods Clinical and related examinations were performed in two pedigrees (21 members including 8 patients) which manifested cerebellar ataxia, loss of color discrimination, decreased visual acuity, etc. The size of the (CAG)n array located in the encode region of SCA7 gene was analyzed for 21 samples from the pedigrees and 55 normal controls through PCR, polyacrylamide gel electrophoresis and related techniques. Results Analysis of 11 parent-child couples demonstrated the existence of marked anticipation, which was greater in paternal than in maternal transmissions, with earlier age of onset and a more rapid clinical course in successive generations. Normal SCA7 alleles carry from 9 to 18 CAG repeats, whereas pathological alleles carry from 44 to 85. There were no subjects with intermediate aize between the normal and affected groups. A subclinical case has been detected by analysis of (CAG) n array. The significant negative correlation was noted between the age of onset and the CAG repeat length, and the larger repeat size seemed to be associated with the more rapid course. Repeat length of expanded alleles showed somatic mosaicism in leukocyte DNA. Conclusion SCA7 pedigrees have been determined in the Chinese, and the clinical features have been clarified. The intergenerational increase in number of CAG repeat units was associated with the clinical phenomenon of anticipation.

关 键 词：橄榄体桥脑小脑萎缩 视网膜变性 等位基因 

分 类 号：R741.02[医药卫生—神经病学与精神病学]