脊髓小脑共济失调第7型的临床特征及基因突变研究

HEREDITAS (Beijing) 2007年6月, 29(6): 688―692 ISSN 0253-9772

研究报告

收稿日期: 2006−09−14; 修回日期: 2006−11−12

基金项目: 浙江省科技厅项目(编号: 2005C33011)和浙江省卫生厅项目(编号: 2005A044)[Supported by Science and Technology Department of Zhejiang Province (No.2005C33011) and Health Bureau Zhejiang Province (No.2005A044)]

作者简介: 殷鑫浈(1979−), 女, 浙江诸暨人, 硕士, 住院医生, 研究方向: 神经遗传性疾病。E-mail: xinzhen_yin@ 通讯作者: 张宝荣(1963−), 男, 浙江仙居人, 博士, 教授,研究方向: 神经遗传性疾病。E-mail: brzhang@

DOI: 10.1360/yc-007-0688

脊髓小脑共济失调第7型的临床特征及基因突变研究

殷鑫浈1, 张宝荣1, 吴鼎文2, 田均1, 张灏1

1. 浙江大学医学院附属第二医院神经内科, 杭州 310009;

2. 中南大学医学遗传学国家重点实验室, 长沙 410078

摘要: 对一脊髓小脑性共济失调(Spinocerebellar ataxia, SCA)家系的患者进行临床特征及相关基因突变研究。对该家系进行详细的病史采集, 并对患者行视力、眼底血管造影、眼底拍照、视觉诱发电位、视网膜电图以及头颅MRI 等辅助检查; 采用聚合酶链反应分别扩增SCA1、SCA2、SCA3、SCA6、SCA7、SCA17及DRPLA 基因的CAG 重复序列, 用8%变性聚丙烯酰胺凝胶电泳及直接测序进行突变分析。结果2名患者主要表现为小脑性共济失调、视力下降、眼底视网膜色素变性、小脑和脑干萎缩; 并存在SCA7基因的突变, 而未发现SCA1、SCA2、SCA3、SCA6、SCA17及DRPLA 基因突变。说明该家系为SCA7突变家系, SCA7基因中CAG 三核苷酸重复拷贝数的异常扩增是其致病原因。

关键词: 脊髓小脑性共济失调第7型; 视网膜变性; 基因突变

The clinical features and gene mutation analysis in a pedigree of spinocerebellar ataxia type 7

YIN Xin-Zhen 1, ZHANG Bao-Rong 1, WU Ding-Wen 2, TIAN Jun 1, ZHANG Hao 1

1. Department of Neurology , the Second Affiliated Hospital , Zhejiang University School of Medicine , Hangzhou 310009, China ;

2. National Lab of Medical Genetics of China , Central South University, Changsha 410078, China

Abstract : We investigated the clinical features and gene mutation in a pedigree of spinocerebellar ataxia (SCA). A series

of clinical tests was performed including visual examination, retinal angiography, visual evoked potential, electroretinogram and magnetic resonance imaging. Genomic DNA of the family members and normal controls was used for amplification of the (CAG)n repeats of SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA genes by PCR. The number of (CAG)n was determined by 8% denaturing polyacrylamide gel electrophoresis and direct sequencing. The main features of 2 patients were ataxia, visual failure, retinal degeneration, cerebellar and pontine atrophy. A mutation in SCA7 gene was detected, while no mutations were found in SCA1, SCA2, SCA3, SCA6, SCA17 or DRPLA gene. Therefore, this is a pedigree of SCA7. Analysis of the CAG trinucleotide repeat expansion at the SCA7 locus can provide valuable insights into SCA7.

Keywords: spinocerebellar ataxia-7; retinal degeneration; gene mutation

脊髓小脑共济失调(spinocerebellar ataxia, SCA)是一种常染色体显性遗传神经系统变性疾病, 主要以小脑性共济失调为主要特征。临床症状复杂, 交

错重叠, 即使在同一家系中也可表现为高度异质性, 分型及鉴别诊断困难。目前已有部分SCA 亚型的致病基因已被定位及克隆, 并已证实基因编码区内的