脊髓小脑型共济失调6型患者的临床特征及基因突变分析

Analysis of the clinical features and genetic mutation of spinocerebellar ataxia type 6 from Chinese kindreds

目的研究脊髓小脑型共济失调(SCA)6型的临床特征和基因突变频率。方法采用聚合酶链反应(PCR)、聚丙烯酰胺凝胶电泳(PAGE)等技术,对160个SCA家系330例患者和77例散发SCA患者进行SCA6(CAG)n的重复数分析,对异常等位基因进行测序;并对SCA6患者进行临床及MRI检查。结果检测确定4个SCA6家系6例患者SCA6(CAG)n的重复数为25和26,正常人群SCA6(CAG)n的重复数为5～17,SCA6突变频率为本组SCA家系的2.5%。SCA6患者临床仅表现为缓慢进展的小脑性共济失调,MRI显示单纯小脑萎缩。结论SCA6是中国SCA中的少见亚型,SCA6与其他SCA亚型有不同的临床及影像学特征。

Objective To study the clinical features and genetic mutation frequency of spinocerebellar ataxia （SCA） type 6 from Chinese kindreds. Methods The SCA6 （CAG） n trinucleotide repeat mutations were detected using polymerase chain reaction （PCR） and polyacrylamide gel electrophoresis （ PAGE ） techniques in 330 patients with autosomal dominant SCA from 160 kindreds and 77 sporadic SCA patients, and the abnormal alleles fragments were sequenced by AB1377 DNA sequencing machine. The clinical features were assessed and cranial MRI examinations were performed in these patients. Results 6 patients from 4 SCA6 Chinese kindreds had abnormal SCA6 alleles with CAG repeat expanded to 25 and 26, respectively, of which 2. 5% was about the positive rate, while CAG repeat of normal SCA6 allele ranged from 5 to 17. The basic characteristics of SCA6 patients were slowly progressive cerebellar ataxia and purely cerebellar atrophy. Conclusion SCA6 is one seldom subtype of SCA in Chinese patients with its characteristics both in clinic and imaging in contrast to other subtypes.