Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds
Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds
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DOI：
10.1001/archneur.57.4.540
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发表时间：
2000-04-01
影响因子：
--
通讯作者：
Xia, JH
中科院分区：
文献类型：
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作者：
Tang, BS;Liu, CY;Xia, JH
目的：探讨脊髓小脑性共济失调1型（SCA 1）的发病率。SCA2. SCA 3/MjD（脊髓小脑性共济失调3型/Machado-Joseph病）、SCA 6、SCA 7。关于DRPLA I（齿状核红核苍白球路易氏体萎缩）CAG三核苷酸重复扩增[（CAG）n]在中国家族遗传性SCA患者中的应用。采用聚合酶链反应、高变性聚丙烯酰胺凝胶电泳、PCR方法检测脊髓小脑共济失调成熟1、SCA 2、SCA 3/MJD、SCAB、SCA 7和DRPLA（CAG）n突变，和银染技术对85个中国家系的167例常染色体显性遗传SCA患者和37例散发SCA患者进行检测。脊髓小脑共济失调I型（CAG）n突变由4个重复（4.70%）扩展到53 ~ 62个重复。IZ患者脊髓小脑性共济失调2型（CAG）n突变由5个重复（5.88%）扩大到42 ~ 47个重复。脊髓小脑共济失调3型/马查多-约瑟夫病（CAG）n突变83例，占48.23%。35例心肌梗死患者和37例散发性SCA患者中65例（41.19%）SCAI检测阴性。SCA 2、SCA 3/MJD、SCA 6、SCAT或DRPLA。SCA 3/MJD和SCA 2的CAG重复次数与发病年龄之间存在可预测的负相关。临床上痴呆和反射减退在SCA 2患者中更常见，而痉挛、反射亢进和巴宾斯基征在SCA 3/MJD患者中更常见。结论：在中国非葡萄牙血统的常染色体显性遗传SCA患者中，SCA 3/MJD的频率明显高于SCA 1和SCA 2。各种类型SCA的临床表现相互重叠，因此，对SCA患者进行基因诊断和基因分型对于临床研究非常重要。
Objective: To assess the frequency of SCA1 (spinocerebellar ataxia type 1). SCA2. SCA3/MjD (spinocerebellar ataxia type 3/Machado-Joseph disease), SCA6, SCA7. and DRPLA I (dentatorubropallidoluysian atrophy) CAG trinucleotide repeat expansions [(CAG)n] among persons diagnosed with hereditary SCA from Chinese families.Patients and Methods: Spinocerebellar ataxia ripe 1, SCA2 SCA3/MJD, SCAB, SCA7, and DRPLA (CAG)n mutation were detected with the polymerase chain reaction, highly denaturing polyacrylamide gel electrophoresis, and silver staining technique in 167 patients with autosomal dominant SCA from 85 Chinese families and 37 patients with sporadic SCA.Results: Spinocerebellar ataxia type I (CAG)n mutation in 7 patients from 4 kindreds (4.70%) was expanded to 53 to 62 repeats. Spinocerebellar ataxia type 2 (CAG)n mutation in IZ patients from 5 kindreds (5.88%) was expanded to 42 to 47 repeats. Spinocerebellar ataxia type 3/Machado-Joseph disease (CAG)n mutation in 83 patients from 41 kindreds (48.23%) was expanded to 68 to 83 repeats. Sixty-five patients from 35 kindreds (41.19%) and 37 patients with sporadic SCA did not test positive for SCAI. SCA2, SCA3/MJD, SCA6, SCAT, or DRPLA. There uas a predictable inverse relationship between the number of CAG repeats and the age at onset for SCA3/MJD and SCA2. Clinically. dementia and hyporeflexia were more frequent in patients with SCA2, while spasticity, hyperreflexia, and Babinski signs were more frequent in patients with SCA3/MJD. and those might be helpful in clinical work to primarily distinguish patients with SCA3/MJD and SCA2 from others with different types of SCA.Conclusions: The frequency of SCA3/MJD is substantially higher than that of SCA1 and SCA2 in patients with autosomal dominant SCA from Chinese kindreds, who are non-Portuguese. Clinical expressions of the various types of SCAs overlap one another; therefore, for clinical study it is important to make a gene diagnosis and genetic classification for patients with SCA.