Frequency analysis of autosomal dominant cerebellar ataxias in Taiwanese patients and clinical and molecular characterization of spinocerebellar ataxia type 6
Frequency analysis of autosomal dominant cerebellar ataxias in Taiwanese patients and clinical and molecular characterization of spinocerebellar ataxia type 6
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DOI：
10.1001/archneur.58.7.1105
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发表时间：
2001-07-01
影响因子：
--
通讯作者：
Lee, HY
中科院分区：
文献类型：
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作者：
Soong, BW;Lu, YC;Lee, HY
背景：脊髓小脑性共济失调（SCA）是一种异质性的神经退行性疾病。大多数这些疾病的突变基础是在所涉及基因编码区域内扩展的CAG重复序列。SCA在台湾华人中的流行程度尚不清楚。此外，在中国人中没有SCA6型（SCA6）的报道。目的：了解台湾华人SCA的患病率，并从临床和分子特征方面明确中国sc6患者的特征。病患与方法：本研究以分子方法研究74个台湾显性遗传性共济失调家族与49个台湾散发性共济失调病患的SCA。对来自8个家庭的12例患者和2例散发病例的临床和分子特征进行了进一步的分析。利用聚合酶链反应扩增基因内多态性标记D19S1150，分析其连锁不平衡。结果：macha多- joseph病（sca3）是台湾队列中最常见的常染色体显性SCA类型，占35例（47.3%），其次是SCA6（8例[10.8%]）、SCA2（8例[10.8%]）、SCA1（4例[5.4%]）、SCA7（2例[2.7%]）、齿状体白斑萎缩（1例[1.4%]）和SCA8（0%）。16例（21.6%）台湾人显性遗传性SCA病例的基因仍有待确定。在本系列的49例散发性共济失调患者中，发现2例（4.1%）携带SCA6突变。在患有SCA6的家庭中，我们发现在没有遗传不稳定性的情况下存在显著的预期，这表明可能有其他机制解释了这种预期。10个台湾sc6家族中有7个家族具有相同的基因内标记（D19S1150）。结论：虽然到目前为止，在中国大陆还没有SCA6的报道，但我们在台湾发现了SCA6家族的地理集群。基因分型研究提示台湾SCA6患者存在奠基者效应。
Background: Spinocerebellar ataxia (SCA) is a heterogeneous group of neurodegenerative disorders. The mutational basis for most of these disorders is an expanded CAG repeat sequence within the coding regions of the genes involved. The prevalence of SCA in the ethnic Chinese on Taiwan remains unclear. Moreover, there has been no report of SCA type 6 (SCA6) among Chinese people.Objectives: To characterize the prevalence of SCA in the ethnic Chinese on Taiwan, and to specifically characterize Chinese patients with SCA6 in terms of clinical and molecular features.Patients and Methods: Using a molecular approach, we investigated SCA in 74 Taiwanese families with dominantly inherited ataxias and in 49 Taiwanese patients with sporadic ataxias. Clinical and molecular features of SCA6 were further characterized in 12 patients from 8 families and in 2 sporadic cases. Furthermore, the intragenic polymorphic marker D19S1150 was amplified by polymerase chain reaction to analyze for linkage disequilibrium.Results: Machado-Joseph disease-SCA3 was the most common type of autosomal dominant SCA in the Taiwanese cohort, accounting for 35 cases (47.3%), followed by SCA6 (8[10.8%]), SCA2 (8[10.8%]), SCA1 (4 [5.4%]), SCA7 (2 [2.7%]), dentatorubropallidoluysian atrophy (1 [1.4%]), and SCA8 (0%). The genes responsible for 16 (21.6%) of Taiwanese dominantly inherited SCA cases remain to be determined. Among the 49 patients with sporadic ataxias in the present series, 2 (4.1%) were found to harbor SCA6 mutations. In the families with SCA6, we found significant anticipation in the absence of genetic instability on transmission, indicating that some other mechanism might account for the anticipation. The same frequent allele of the intragenic DNA marker (D19S1150) was shared by 7 of 10 Taiwanese families with SCA6.Conclusions: Although SCA6 has, so far, not been reported in mainland Chinese, we found a geographic cluster of families with SCA6 on Taiwan. Genotyping studies suggest a founder effect in the Taiwanese patients with SCA6.