Experimental Neurology, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
Neurobiol Dis. 2012 Jan;45(1):356-61. doi: 10.1016/j.nbd.2011.08.021. Epub 2011 Aug 25.
Full expansions of the polyglutamine domain (polyQ≥34) within the polysome-associated protein ataxin-2 (ATXN2) are the cause of a multi-system neurodegenerative disorder, which usually presents as a Spino-Cerebellar Ataxia and is therefore known as SCA2, but may rarely manifest as Levodopa-responsive Parkinson syndrome or as motor neuron disease. Intermediate expansions (27≤polyQ≤33) were reported to modify the risk of Amyotrophic Lateral Sclerosis (ALS). We have now tested the reproducibility and the specificity of this observation. In 559 independent ALS patients from Central Europe, the association of ATXN2 expansions (30≤polyQ≤35) with ALS was highly significant. The study of 1490 patients with Parkinson's disease (PD) showed an enrichment of ATXN2 alleles 27/28 in a subgroup with familial cases, but the overall risk of sporadic PD was unchanged. No association was found between polyQ expansions in Ataxin-3 (ATXN3) and ALS risk. These data indicate a specific interaction between ATXN2 expansions and the causes of ALS, possibly through altered RNA-processing as a common pathogenic factor.
在多核糖体相关蛋白 ataxin-2（ATXN2）中，聚谷氨酰胺结构域（polyQ≥34）的完全扩展是一种多系统神经退行性疾病的原因，通常表现为脊髓小脑共济失调，因此称为 SCA2，但很少表现为左旋多巴反应性帕金森综合征或运动神经元病。中间扩展（27≤polyQ≤33）被报道会改变肌萎缩侧索硬化症（ALS）的风险。我们现在已经测试了这一观察结果的重现性和特异性。在来自中欧的 559 名独立 ALS 患者中，ATXN2 扩展（30≤polyQ≤35）与 ALS 的关联具有高度显著性。对 1490 名帕金森病（PD）患者的研究表明，在具有家族病例的亚组中，ATXN2 等位基因 27/28 丰富，但散发性 PD 的总体风险不变。在 Ataxin-3（ATXN3）中的 polyQ 扩展与 ALS 风险之间未发现关联。这些数据表明 ATXN2 扩展与 ALS 病因之间存在特定的相互作用，可能通过改变 RNA 处理作为共同的致病因素。
