中国汉族人群CACNA1A基因CAG重复数目分布特点及其在脊髓小脑性共济失调6型基因诊断中的应用

目的 探讨我国汉族人群CACNA1A基因CAG重复数目分布特点及其在脊髓小脑性共济失调6型(spinocerebellar ataxias type 6,SCA6)基因诊断中的应用.方法 应用"两步PCR法"、变性聚丙烯酰胺凝胶电泳(DPAGE)和测序等方法对300名健康对照及109例无血缘关系的SCA患者进行CACNA1A基因CAG三核苷酸重复数目分析.结果 300名健康对照的CAG重复次数范围为3～18次,以13次最常见.在109例SCA患者中,发现1例SCA6患者,其CAG异常重复次数为24次,该患者的母亲和哥哥亦为SCA6患者,临床上均表现为缓慢进展的小脑性共济失调、构音障碍、眼震、轻度的振动及本体觉减退,遗传早现现象较明显.结论 SCA6病例在我国较少见,进行CACNA1A基因突变分析有助于临床诊断."两步PCR法"可提高CACNA1A基因突变分析的效率.

The characteristics of CAG repeat in the CACNA1A gene in the Chinese Han population and its application in molecular diagnosis of spinocerebellar ataxia type 6

Objective To investigate distribution of CAG repeat in the CACNA1A gene in theChinese Han population and its application in molecular diagnosis of spinocerebellar ataxia type 6(SCA6).Methods The trinucleotide repeats of CAG were detected by two-step polymerase chain reaction(PCR).denaturing polyacrylamide gel electrophoresis(DPAGE)and DNA sequencing in 300 normal individuals and 109 unrelated SCA patients.Results In normal individuals.the number of CAG repeats ranged from 3 to 18 with 13 being the most frequent repeats.In 109 SCA patients,one patient was identified of 24 repeats and was diagnosed with SCA6.This patient's mother and elder brother were also SCA6 patients.They all showed slowly progressive cerebellar ataxia,dysarthria,nystagmus,minor impairment in vibration sensation and proprioeeptive sensation in clinical manifestation with obvious anticipation.Conclusions SCA6 is rare in the Chinese Population.Mutation analysis of the CACNA1A gene is helpful for clinical diagnosis of SCA6.Two-step PCR increases the efficieney of molecular diagnosis in SCA6.