摘要
目的 研究中国人遗传性脊髓小脑型共济失调 6型 (SCA6)的基因突变和临床特征。方法 应用聚合酶链反应 (PCR)、聚丙烯酰胺凝胶电泳 (PAGE)等技术 ,检测临床诊断脊髓小脑型共济失调 (SCA)的 1 2 0个家系 2 1 0例患者和 47例散发SCA患者的SCA6基因内CAG三核苷酸重复序列 ,并对异常等位基因片段进行DNA测序。结果 检出 2个家系 (4例患者 )为SCA6 ,阳性率为1 7% ,测序证实其异常等位基因的CAG重复数目为 2 5和 2 6。另 2 53例SCA患者的SCA6等位基因CAG重复数目为 7～ 1 7,健康人SCA6等位基因CAG重复数目为 5～ 1 6。 2个家系均存在遗传早现现象 ,异常扩展的CAG序列呈代间稳定性。结论 从临床及基因诊断方面首次确认中国大陆存在SCA6家系 ;
Objective To study the gene mutation and clinical characteristics of hereditary spinocerebellar ataxia type 6 (SCA6) from two Chinese families Methods The SCA6 (CAG)n trinucleotide repeat mutations were detected using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) technique in 210 patients with autosomal dominant SCA from 120 families and 47 sporadic SCA patients,and 50 healthy persons were used as controls. The abnormal allele fragments were sequenced by ABI 377 DNA sequencing machine Results Two SCA families (four patients) had abnormal SCA6 alleles with the CAG repeat expanded to 25 and 26 repeats respectively, as confirmed by DNA sequencing, of which 1.7% (2/120 ) was about the positive rate. Normal SCA6 alleles were carried from 5 to 16 CAG repeats, whereas pathological alleles carry 7 to 17. Analysis of parent child couples demonstrated the existence of marked anticipation with earlier age of onset and a more rapid clinical course in successive generations. The intergenerational stability was noted in the number of CAG repeat. Conclusions Two SCA6 pedigrees have been firstly determined in Chinese from the clinical and genomic aspects. CAG expansions were suggested as the pathogenic cause of SCA6.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2003年第2期98-101,共4页
Chinese Journal of Neurology
基金
国家自然科学基金资助项目( 30 0 70 2 73)
国家高技术研究发展计划( 86 3计划)资助项目( 2 0 0 1AA2 2 70 11)
