中国大陆汉族人群SCA各亚型的突变频率分析及SCA6的临床和分子特征

目的评价中国大陆汉族人群常染色体显性遗传脊髓小脑型共济失调(spinocerebellar ataxla．SCA)各亚型包括SCA1、SCA2、SCA3／Machado-Joseph病(Machado—Joseph disease,MJD)、SCA6、SCA7、SCAB、SCA10、SCA12、SCA14、SCA17和齿状核红核苍白球路易氏体萎缩症(dentatorubro—pallidoluysian atrophy，DRPLA)的突变频率，并总结SCA6的临床和分子特征。方法对中国大陆120个常染色体显性遗传SCA家系和60例散发性SCA患者进行突变分析，并总结了4个SCA6家系13例患者的临床和分子特征。结果SCA3／MJD是中国大陆汉族人群中最常见的SCA亚型，共发现59个家系83例患者(阳性率49．2％)．其次还发现8个SCA2家系(6．7％)、7个SCA1家系(5．8％)、4个SCA6家系(3．3％)、1个SCA7家系(0．8％)，未发现SCA8、SCA10、SCA12、SCA14、SCA17和DRPLA家系。有41个SCA家系(34．2％)不能进行基因分型。在60例散发性SCA患者中，有3例为SCA3基因突变，未发现有SCA6基因突变。4个SCA6家系有明显的遗传早现，但在代间传递过程中无遗传不稳定现象。结论首次在中国大陆汉族人群报道了SCA6亚型的突变频率。

Frequency analysis of autosomal dominant spinocerebellar ataxias in Han population in the Chinese mainland and clinical and molecular characterization of spinocerebellar ataxia type 6

Objective To assess the frequency of spinocerebellar ataxia (SCA), including the subtypes of SCA1, SCA2, SCA3/Machado-Joseph disease(MJD), SCA6, SCA7, SCA8, SCA10, SCA12, SCA14, SCA17 and dentatorubro-pallidoluysian atrophy (DRPLA) in Han population in the Chinese mainland, and to specifically characterize the mainland Chinese patients with SCA6 in terms of clinical and molecular features. Methods Using a molecular approach, the authors investigated SCA in 120 families with dominantly inherited ataxias and in 60 patients with sporadic ataxias. Clinical and molecular features of SCA6 were further characterized in 13 patients from 4 families. Results SCA3/MJD was the most common type of autosomal dominant SCA in the Han population, accounting for 83 patients from 59 families(49.2%), followed by SCA2(8,6.7%), SCA1(7,5.8%), SCA6(4,3.3%), SCA7(1,0.8%), SCA8 (0), SCA10 (0), SCA12(0), SCA14 (0), SCA17(0) and DRPLA(0). The genes responsible for 41(34.2%) of dominantly inherited SCA families remained undetermined. Among the 60 patients with sporadic ataxias in the present series, 3(5.0%) were found to harbor SCA3 mutations while none were found to harbor SCA6 mutations. In the 4 families with SCA6, significant anticipation was found with no genetic instability on transmission. Conclusion The present authors firstly found and reported a geographic cluster of families with SCA6 subtype in the Chinese mainland, which were initially identified in Hans reported of the Chinese mainland.