Age at onset variance analysis in spinocerebellar ataxias:: A study in a Dutch-French cohort
Age at onset variance analysis in spinocerebellar ataxias:: A study in a Dutch-French cohort
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DOI：
10.1002/ana.20424
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发表时间：
2005-04-01
影响因子：
11.2
通讯作者：
Kremer, BPH
中科院分区：
文献类型：
--
作者：
Warrenburg, BPCV;Hendriks, H;Kremer, BPH
在显性脊髓小脑性共济失调 (SCAs) 中，非 CAG 依赖性因素是否会影响发病年龄的问题仍悬而未决。 802 名患者获得了有关 SCA 基因型、发病年龄、正常/扩展的 CAG 重复长度、患者性别和传播父母以及家庭详细信息的数据。基于模型 [log,0（发病年龄）= k - CAG(exp) + epsilon]，我们检查了在该模型中纳入其他因素后调整后的 R-2 和残余标准误差的变化。扩大的重复解释了 44.3% 至 74.9% 的发病年龄差异，尽管在 SCA3 和 SCA6 中这一比例低于 50%，这意味着非 CAG 因素的影响很大。对于 SCA1、3、6 和 7，发病年龄与 CAG 重复之间的关系相似，但对于 SCA2 不同，这表明 SCA2 中的多谷氨酰胺效应不同。对于 SCA2 和 SCA3，目前（未确定的）家族因素分别解释了 17.1% 和 45.5% 的发病年龄差异。我们发现 SCA1 和 SCA6 中非扩展等位基因的显着贡献。除了聚谷氨酰胺基序（由扩展的 CAG 重复长度确定）之外，我们还确定了以下发病年龄修饰因子：SCA2 中的蛋白质背景； SCA2 和 SCA3 的家族因素；以及 SCA1 和 SCA6 中的非扩展 CAG 重复序列。
In dominant spinocerebellar ataxias (SCAs), the issue of whether non-CAG dependent factors contribute to onset age remains unsettled. Data on SCA genotype, onset age, normal/expanded CAG repeat length, sex of the patient and transmitting parent, and family details were available from 802 patients. Based on the model [log,0 (age at onset) = k - CAG(exp) + epsilon], we examined changes in adjusted R-2 and residual standard error following incorporation of the other factors in this model. The expanded repeat explained 44.3 to 74.9% of onset age variance, although this was less than 50% in SCA3 and SCA6, implicating a large effect of non-CAG factors. The relation between onset age and CAG repeat was similar for SCA1, 3, 6, and 7, but different for SCA2, pointing to different polyglutamine effects in SCA2. For SCA2 and SCA3, 17.1 and 45.5% of onset age variance, respectively, were explained by currently (unidentified) familial factors. We found a significant contribution of the nonexpanded allele in SCA1 and SCA6. Besides polyglutamine motif (determined by the expanded CAG repeat length), we identified the following age at onset modifiers: protein context in SCA2; familial factors in SCA2 and SCA3; and the nonexpanded CAG repeat in SCA1 and SCA6.