中文摘要：

目的 研究中国汉族健康人群中脊髓小脑性共济失调（spinocerebellar ataxias,SCA）1、2、3、6、7、8、10、12、17亚型和齿状核红核苍白球路易体萎缩（dentatorubral-pallidoluysian atrophy,DRPLA）亚型致病基因多核苷酸正常重复次数的范围,以助于SCA各亚型基因诊断平台的建立和诊断标准的确认.方法 应用荧光聚合酶链反应、毛细管凝胶电泳等技术对300名健康个体进行SCA 1、2、3、6、7、8、10、12、17亚型和DRPLA亚型致病基因多核苷酸正常重复次数的检测分析.结果 在300名健康个体中CAG三核苷酸在SCA1亚型中为17～35次,在SCA2亚型中为14～28次,在脊髓小脑性共济失调3型/Machado-Joseph病,SCA3/Machado-Joseph disease,SCA3/MJD亚型中为13～41次,在SCA6亚型中为4～16次,在SCA7亚型中为5～17次,在SCA12亚型中为5～21次,在SCA17亚型中为23～41次,在DRPLA亚型中为12～33次;在SCA8亚型中CTA/CTG三核苷酸的重复次数为12～43次;在SCA10亚型中ATTCT五核苷酸的重复次数为9～32次.其中SCA8的12次CTA/CTG三核苷酸重复,SCA10的9次ATTCT五核苷酸重复,SCA17的23次CAG三核苷酸重复,为目前国内外报道的3种亚型多核苷酸正常重复次数的最小次数.SCA3/MJD亚型的41次CAG三核苷酸重复,SCA10亚型的32次ATTCT五核苷酸重复为目前报道的2种亚型多核苷酸正常重复次数的最大次数.结论 SCA各亚型多核苷酸正常次数范围存在种族差异,与遗传和种族背景相关;首次建立了中国汉族人群10种不同SCA亚型正常核苷酸重复次数范围,可为SCA的诊断提供参考标准.

英文摘要：

Objective To assist the establishment of platform and provide the reference standard for mutation detection in spinocerebellar ataxia （SCA） subtypes 1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubralpallidoluysian atrophy （DRPLA） in Chinese Han population. Methods The nucleotide repeat numbers of the 9 SCA subtypes and DRPLA were detected using fluorescence-PCR and capillary gel electrophoresis technique in 300 healthy Chinese Han individuals. Results Among the 300 healthy controls, the range of the CAG trinucleotide repeat number was 17 to 35 in SCA1,14-28 in SCA2, 13-41 in SCA3/MJD, 4-16 in SCA6, 5-17 in SCA7, 5-21 in SCA12, 23-41 in SCA17, and 12-33 in DRPLA; and the range of CTA/CTG trinucleotide repeat number on SCA8 locus was 12-43 and the range of ATTCT pentanucleotide repeat number on SCA10 locus was 9-32. Of which, the 12 CTA/CTG repeats of SCA8, 9 ATTCT repeats of SCA10, 23 CAG repeats of SCA17 were the shortest normal repeat number, while the 41 CAG repeats of SCA3/MJD, 32 CAG repeats of SCA10 were the largest normal number that have not been reported. Conclusion The normal ranges of polynucleotide repeats of different subtypes of SCA vary with geographical areas and ethnicities. It might be associated with the genetic and ethnic backgrounds. This is the first normal reference standard of polynucleotide repeat number of these ten SCA subtypes in Chinese Han.