中国大陆南方汉族正常人群齿状核红核苍白球路易体萎缩基因三核苷酸重复变异研究

目的研究中国大陆南方正常人群齿状核红核苍白球路易体萎缩(DRPLA)基因(以CAG)n正常变异范围,以及DRPLA基因(CAG)n扩展突变在中国大陆脊髓小脑型共济失调(SCA)患者中的分布。方法应用荧光PCR,毛细管电泳等技术,对67个已经排除了SCA1、SCA2、SCA3、SCA6、SCA7的常染色体显性遗传SCA家系的先证者和66个散发SCA患者以及94个南方正常汉族人进行DRPLA基因CAG重复次数分析。结果未发现DRPLA基因(CAG)n扩展突变；DRPLA基因(CAG)n正常变异范围为5～21个拷贝,15个拷贝最多见,杂合频率为89．13%,共14种等位基因。结论DRPLA在中国大陆为罕见的SCA亚型,DRPLA基因(CAG)n正常变异范围存在地区和种族差异,中国大陆DRPLA发病率低可能同正常国人较大重复次数的等位基因少见有关。

Research on the normal range of CAG repeats of dentatorubropallidoluysian atrophy gene in Han population of South China mainland

Objective To study the normal range of CAG repeats of dentatorubropallidoluysian atrophy (DRPLA) gene in Han population of South China mainland,and the frequency of DRPLA CAG trinucleotide repeat expansion in spinocerebellar ataxia(SCA) of China mainland.Methods The CAG repeats of DRPLA gene were detected using fluorescence-PCR and capillary electrophoresis technique in 67 probands of autosomal dominant familial SCA and 66 sporadic SCA patients without CAG repeat expansion at the SCA1,SCA2,SCA3,SCA6,SCA7 loci,and 94 healthy persons as controls.Results The size of normal alleles varied from 5 to 21 repeats.There were 14 alleles,with the 15-repeat allele having the maximum frequency,and heterozygosity was 89.13%.Conclusion DRPLA is a rare subtype of SCA in China mainland.The normal ranges of CAG repeats of DRPLA gene vary with areas and races.The low prevalence of DRPLA seems to be correlated with the low frequency of large normal alleles in China populations.