中国汉族人群ATXN8OS基因CTA／CTG三核苷酸重复研究

Studies on the CTA/CTG trinucleotide repeats of ATXN8OS gene in Chinese Hans

目的研究中国正常人群脊髓小脑性共济失调（spinocerebellar ataxia，SCA）8型（SCA8）致病基因ATXN8OS（CTA／CTG）n正常变异范围，以及ATXN8OS基因（CTA／CTG）n扩展突变在中国大陆SCA患者中的分布。方法应用荧光PCR、8％变性聚丙烯酰胺凝胶电泳和毛细管凝胶电泳等方法对132例已经排除SCA1、SCA2、SCA3、SCA6、SCA7、SCA12、SCA17和齿状核红核苍白球路易体萎缩（dentatorubral—pallidoluysian atrophy，DRPLA）的SCA患者及261名正常汉族对照人群进行AIXN8OS基因三核苷酸重复次数分析。结果未发现ATXN8OS基因（CTA／C3G）n核苷酸扩展突变；132例SCA患者中ATXN8OS基因（CTA／CTG）n变异范围为17～47次，平均重复次数（24．20＋4．57）次，18次重复最常见，纯合子35例，纯合率为26．5％；261名正常对照人群ATXN8OS基因（CTA／CTG）n正常变异范围为12．43次，均重复次数（24．04＋4．53）次，18次重复最常见，纯合子70人，纯合率为26．8％。结论SCA8在中国大陆为罕见的SCA亚型，中国大陆SCA8发病率低可能和正常人群较大（CTA／CTG）n重复次数的等位基因少见有关。

Objective To study the normal range of （CTA/CTG）n repeats of ATXN8OS gene in Chinese Hans, and the frequency of ATXN8OS （ CTA/CTG）n repeat expansion in spinocerebellar ataxia（ SCA ） patients in China's Mainland. Methods The （CTA/CTG）n repeats ofATXN80S gene were detected using fluorescence-PCR, 8% denaturing polyacrylamide gel and capillary electrophoresis technique in 132 SCA patients in whom CAG expansion at the SCA1, SCA2, SCA3, SCA6, SCA7, SCA12, SCA17 and dentatorubral-pallidoluysian atrophy（DRPLA） loci has been excluded, and 261 healthy controls. Results There were no obvious abnormal changes of the （CTA/CTG）n repeats of ATXN8OS gene in the 132 SCA patients. Thirty-five SCA patients were homozygotes （26.5%）, and the range of CTA/ CTG repeat number was 17 to 47 （24.20 ± 4.57）, among which 18 repeats appeared most frequently. In 261 normal controls, 70 were homozygotes （26.8%）, and the range of the CTA/CTG repeat number was from 12 to 43 （24.04 ± 4.53）, among which 18 repeats was the most frequent. Conclusion SCA8 is a rare subtype of SCA in China's Mainland. The low prevalence of SCA8 seems to he correlated with the low frequency of large （CTA/CTG）n copy number alleles in Chinese population.