Sinke R J, Ippel E F, Diepstraten C M, Beemer F A, Wokke J H, van Hilten B J, Knoers N V, van Amstel H K, Kremer H P
Department of Medical Genetics, University Medical Center Utrecht, KC04.084.2, PO Box 85090, 3508 AB Utrecht, The Netherlands.
Arch Neurol. 2001 Nov;58(11):1839-44. doi: 10.1001/archneur.58.11.1839.
Autosomal dominant cerebellar ataxias (ADCAs), or spinocerebellar ataxias (SCAs), are a heterogeneous group of neurodegenerative disorders. Mild CAG repeat expansions in the alpha(1A) voltage-dependent calcium channel gene are associated with SCA type 6 (SCA6).
To obtain further insight into the contribution of SCA6 mutations to the phenotypic variability in Dutch patients with ataxia.
Survey and case series.
Hospitalized care, referral center.
The SCA6 locus was analyzed for CAG repeat expansions in a referred sample of 220 Dutch families with progressive cerebellar ataxia. Clinical characteristics of patients with SCA6 were investigated and correlated with molecular findings.
The diagnosis SCA6 was confirmed in 24 families comprising 30 familial and 4 sporadic cases. Mean +/- SD age at onset was 50.1 +/- 11.1 years. Expanded CAG repeats with sizes 22, 23, and 25 were found. These sizes correlated inversely with age at onset. No intergenerational changes in CAG repeat size were detected. Despite this, 2 families showed clinical anticipation.
This study provides the first detailed description of Dutch patients with SCA6. Clinical analysis identifies SCA6 as a late-onset ataxia in which eye movement abnormalities are prominent and consistent early manifestations. No single clinical sign can be considered specific for SCA6. Some patients have ataxia combined with episodic headaches or nausea, suggesting an overlap among SCA6, eposidic ataxia type 2, and familial hemiplegic migraine. Spinocerebellar ataxia type 6 accounts for approximately 11% of all Dutch families with ADCA. Analysis of SCA6 contributes further to the genetic classification of patients with ADCA, including patients without a clear family history of the disease.
常染色体显性遗传性小脑共济失调（ADCA），即脊髓小脑共济失调（SCA），是一组异质性神经退行性疾病。α1A电压依赖性钙通道基因中轻度的CAG重复序列扩增与6型脊髓小脑共济失调（SCA6）相关。
进一步了解SCA6突变对荷兰共济失调患者表型变异性的影响。
调查与病例系列研究。
住院护理、转诊中心。
对220个患有进行性小脑共济失调的荷兰家庭的转诊样本进行SCA6位点CAG重复序列扩增分析。对SCA6患者的临床特征进行研究，并与分子学结果进行关联分析。
在24个家庭中确诊为SCA6，包括30个家族性病例和4个散发性病例。平均发病年龄±标准差为50.1±11.1岁。发现CAG重复序列扩增大小为22、23和25，这些大小与发病年龄呈负相关。未检测到CAG重复序列大小的代际变化。尽管如此，有2个家庭表现出临床遗传早现现象。
本研究首次对荷兰SCA6患者进行了详细描述。临床分析确定SCA6为晚发性共济失调，其中眼球运动异常是突出且一致的早期表现。没有单一临床体征可被认为是SCA6所特有的。一些患者的共济失调合并发作性头痛或恶心，提示SCA6、2型发作性共济失调和家族性偏瘫性偏头痛之间存在重叠。6型脊髓小脑共济失调约占所有荷兰ADCA家庭的11%。对SCA6的分析进一步有助于ADCA患者的基因分类，包括无明确家族病史的患者。
