PDF(Pubmed)
Abstract：
Cerebellar syndromes are clinically and etiologically heterogeneous and can be classified as hereditary, neurodegenerative non-hereditary, or acquired. Few data are available on the frequency of each form in the clinical setting. Growing interest is emerging regarding the genetic forms caused by triplet repeat expansions. Alleles with repeat expansion lower than the pathological threshold, termed intermediate alleles (IAs), have been found to be associated with disease manifestation. In order to assess the relevance of IAs as a cause of cerebellar syndromes, we enrolled 66 unrelated Italian ataxic patients and described the distribution of the different etiology of their syndromes and the frequency of IAs. Each patient underwent complete clinical, hematological, and neurophysiological assessments, neuroimaging evaluations, and genetic tests for autosomal dominant cerebellar ataxia (SCA) and fragile X-associated tremor/ataxia syndrome (FXTAS). We identified the following diagnostic categories: 28% sporadic adult-onset ataxia, 18% cerebellar variant of multiple system atrophy, 9% acquired forms, 9% genetic forms with full-range expansion, and 12% cases with intermediate-range expansion. The IAs were six in the FMR1 gene, two in the gene responsible for SCA8, and one in the ATXN2 gene. The clinical phenotype of patients carrying the IAs resembles, in most of the cases, the one associated with full-range expansion. Our study provides an exhaustive description of the causes of cerebellar ataxia, estimating for the first time the frequency of IAs in SCAs- and FXTAS-associated genes. The high percentage of cases with IAs supports further screening among patients with cerebellar syndromes.
摘要：
小脑综合征在临床和病因上是异质性的，可以归类为遗传性，神经退行性非遗传性，或获得。关于每种形式在临床环境中的频率的数据很少。关于由三联体重复扩增引起的遗传形式的兴趣日益增加。重复扩增低于病理阈值的等位基因，称为中间等位基因(IA)，已发现与疾病表现有关。为了评估IAs作为小脑综合征病因的相关性，我们纳入了66例非相关的意大利共济失调患者,并描述了他们的综合征的不同病因的分布和IAs的频率.每位患者都接受了完整的临床，血液学,和神经生理学评估，神经影像学评估，常染色体显性遗传小脑共济失调（SCA）和脆性X相关震颤/共济失调综合征（FXTAS）的遗传测试。我们确定了以下诊断类别：28％的偶发性成人共济失调，18％的小脑变异多系统萎缩，9%获得的形式，9％的遗传形式具有全范围扩展，和12%的情况下有中等范围的扩展。IAs在FMR1基因中有6个，两个在负责SCA8的基因中，一个在ATXN2基因中。携带IAs的患者的临床表型相似，在大多数情况下，与全方位扩展相关的。我们的研究详尽描述了小脑共济失调的原因，首次估计SCAS和FXTAS相关基因中IAs的频率。较高比例的IAs病例支持在小脑综合征患者中进行进一步筛查。
