Department of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
Cerebellum. 2013 Apr;12(2):155-61. doi: 10.1007/s12311-012-0403-5.
Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders currently associated with 27 genes. The most frequent types are caused by expansions in coding CAG repeats. The frequency of SCA subtypes varies among populations. We examined the occurrence of rare SCAs, SCA8, SCA12, SCA17 and dentatorubro-pallidoluysian atrophy (DRPLA), in the Czech population from where the data were missing. We analyzed causal gene expansions in 515 familial and sporadic ataxic patients negatively tested for SCA1-3 and SCA6-7. Pathogenic SCA8 and SCA17 expansions were identified in eight and five patients, respectively. Tay-Sachs disease was later diagnosed in one patient with an SCA8 expansion and the diagnosis of multiple sclerosis (MS) was suspected in two other patients with SCA8 expansions. These findings are probably coincidental, although the participation of SCA8 expansions in the susceptibility to MS and disease progression cannot be fully excluded. None of the patients had pathogenic SCA12 or DRPLA expansions. However, three patients had intermediate SCA12 alleles out of the normal range with 36 and 43 CAGs. Amyotrophic lateral sclerosis (ALS) was probable in the patient with 43 CAGs. This coincidence is remarkable, especially in the context with the recently identified predisposing role of longer SCA2 alleles in ALS. Five families with SCA17 represent a significant portion of ataxic patients and this should be reflected in the diagnostics of SCAs in the Czech population. SCA8 expansions must be considered after careful clinical evaluation.
脊髓小脑共济失调（SCAs）是一组异质性的神经退行性疾病，目前与 27 个基因相关。最常见的类型是由编码 CAG 重复扩增引起的。亚型在人群中的频率不同。我们检查了捷克人群中罕见的 SCA、SCA8、SCA12、SCA17 和齿状核红核苍白球路易体萎缩症（DRPLA）的发生情况，这些数据在该人群中是缺失的。我们分析了 515 例家族性和散发性共济失调患者的致病基因扩增情况，这些患者均经 SCA1-3 和 SCA6-7 检测为阴性。在 8 名和 5 名患者中分别发现了致病性 SCA8 和 SCA17 扩增。一名 SCA8 扩增患者后来被诊断为泰萨二氏病，另外两名 SCA8 扩增患者疑似多发性硬化症（MS）。这些发现可能是偶然的，尽管不能完全排除 SCA8 扩增参与 MS 的易感性和疾病进展。没有患者有致病性 SCA12 或 DRPLA 扩增。然而，有 3 名患者的 SCA12 等位基因处于正常范围之外，分别有 36 和 43 个 CAG。43 个 CAG 的患者可能患有肌萎缩侧索硬化症（ALS）。这种巧合引人注目，尤其是在最近发现的较长 SCA2 等位基因在 ALS 中的易感性作用的背景下。有 5 个 SCA17 家系代表了相当一部分共济失调患者，这在捷克人群的 SCA 诊断中应该得到反映。在进行仔细的临床评估后，应考虑 SCA8 扩增。
