van de Warrenburg B P C, Sinke R J, Verschuuren-Bemelmans C C, Scheffer H, Brunt E R, Ippel P F, Maat-Kievit J A, Dooijes D, Notermans N C, Lindhout D, Knoers N V A M, Kremer H P H
Department of Neurology, University Medical Center St. Radboud, Nijmegen, the Netherlands.
Neurology. 2002 Mar 12;58(5):702-8. doi: 10.1212/wnl.58.5.702.
International prevalence estimates of autosomal dominant cerebellar ataxias (ADCA) vary from 0.3 to 2.0 per 100,000. The prevalence of ADCA in the Netherlands is unknown. Fifteen genetic loci have been identified (SCA-1-8, SCA-10-14, SCA-16, and SCA-17) and nine of the corresponding genes have been cloned. In SCA-1, SCA2, SCA3, SCA6, SCA7, SCA-12 and SCA-17 the mutation has been shown to be an expanded CAG repeat. Previously, the length of the CAG repeat was found to account for 50 to 80% of variance in age at onset. Because of heterogeneity in encoded proteins, different pathophysiologic mechanisms leading to neurodegeneration could be involved. The relationship between CAG repeat length and age at onset would then differ accordingly.
Based on the results of SCA mutation analysis in the three DNA diagnostic laboratories that serve the entire Dutch population, the authors surveyed the number of families and affected individuals per SCA gene, as well as individual repeat length and age at onset. Regression analysis was applied to study the relationship between CAG repeat length and age at onset per SCA gene. The slopes of the different regression curves were compared.
On November 1, 2000, mutations were found in 145 ADCA families and 391 affected individuals were identified. The authors extrapolated a minimal prevalence of 3.0 per 100,000 (range 2.8 to 3.8/100,000). SCA3 was the most frequent mutation. CAG repeat length contributed to 52 to 76% of age at onset variance. Regression curve slopes for SCA-1, SCA2, SCA3, and SCA7 did not differ significantly.
The estimated minimal prevalence of ADCA in the Netherlands is 3.0 per 100,000 inhabitants. Except for SCA6, the relationship between age at onset and CAG repeat expansion does not differ significantly between SCA-1, SCA2, SCA3, and SCA7 patient groups in our population, indicating that these SCA subtypes share similar mechanisms of polyglutamine-induced neurotoxicity, despite heterogeneity in gene products.
常染色体显性遗传性小脑共济失调（ADCA）的国际患病率估计为每10万人中有0.3至2.0例。荷兰ADCA的患病率尚不清楚。已确定了15个基因位点（SCA - 1 - 8、SCA - 10 - 14、SCA - 16和SCA - 17），并克隆了其中9个相应的基因。在SCA - 1、SCA2、SCA3、SCA6、SCA7、SCA - 12和SCA - 17中，突变已被证明是CAG重复序列的扩增。此前，发现CAG重复序列的长度占发病年龄变异的50%至80%。由于编码蛋白质的异质性，可能涉及导致神经退行性变的不同病理生理机制。那么CAG重复序列长度与发病年龄之间的关系也会相应不同。
基于为整个荷兰人群服务的三个DNA诊断实验室的SCA突变分析结果，作者调查了每个SCA基因的家系数量和受累个体数量，以及个体的重复序列长度和发病年龄。应用回归分析研究每个SCA基因的CAG重复序列长度与发病年龄之间的关系。比较不同回归曲线的斜率。
2000年11月1日，在145个ADCA家系中发现了突变，共确定了391名受累个体。作者推断最低患病率为每10万人中有3.0例（范围为2.8至3.8/10万）。SCA3是最常见的突变。CAG重复序列长度占发病年龄变异的52%至76%。SCA - 1、SCA2、SCA3和SCA7的回归曲线斜率无显著差异。
荷兰ADCA的估计最低患病率为每10万居民中有3.0例。除SCA6外，在我们的人群中，SCA - 1、SCA2、SCA3和SCA7患者组的发病年龄与CAG重复序列扩增之间的关系无显著差异，这表明尽管基因产物存在异质性，但这些SCA亚型在多聚谷氨酰胺诱导的神经毒性机制上具有相似性。
