Parkinsonian phenotype in Machado-Joseph disease (MJD/SCA3): a two-case report.
Parkinsonian phenotype in Machado-Joseph disease (MJD/SCA3): a two-case report.
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DOI：
10.1186/1471-2377-11-131
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发表时间：
2011-10-24
期刊：
影响因子：
2.6
通讯作者：
Lima M
中科院分区：
文献类型：
--
作者：
Bettencourt C;Santos C;Coutinho P;Rizzu P;Vasconcelos J;Kay T;Cymbron T;Raposo M;Heutink P;Lima M
Machado-Joseph病（MJD）或脊髓小脑共济失调3型（SCA 3）是一种迟发性常染色体显性遗传神经退行性疾病，其由ATXN 3基因编码区的CAG重复扩增引起。这种疾病的临床异质性，这不能完全解释的大小重复道。MJD表现为锥体外系运动体征，即帕金森综合征，比常染色体显性遗传小脑共济失调的其他亚型更常见。虽然帕金森氏症似乎隔离MJD家庭内，只有少数MJD患者发展帕金森氏症的功能，因此，这些罕见的介绍临床和遗传方面的研究仍然很差。这项工作的主要目标是描述两名MJD患者表现出帕金森病三联征（震颤，运动迟缓和僵硬），即帕金森病（PD）相关基因座（PARK 2，LRRK 2，PINK 1，DJ-1，SNCA，MAPT，APOE和mtDNA tRNAGln T4336 C）的遗传变异。 患者1是一名40岁的女性（在30岁时发病），最初具有纯帕金森病表型（类似于先前报道的其母亲的表型）。患者2是一名38岁的男性（在33岁时发病），表现出具有帕金森特征的共济失调表型（在其他受影响的兄弟姐妹或其父亲中均未观察到）。这两名患者提出了一个扩展的ATXN 3等位基因与72 CAG重复。在所分析的基因座中未发现PD突变。然而，在这两名患者的DJ-1和APOE基因中观察到了先前与PD相关的等位基因变异。本报告增加了这种特殊和罕见的MJD介绍的临床和遗传信息，并提出了假设，DJ-1和APOE多态性可能赋予MJD的帕金森病表型的易感性。
Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder of late onset, which is caused by a CAG repeat expansion in the coding region of the ATXN3 gene. This disease presents clinical heterogeneity, which cannot be completely explained by the size of the repeat tract. MJD presents extrapyramidal motor signs, namely Parkinsonism, more frequently than the other subtypes of autosomal dominant cerebellar ataxias. Although Parkinsonism seems to segregate within MJD families, only a few MJD patients develop parkinsonian features and, therefore, the clinical and genetic aspects of these rare presentations remain poorly investigated. The main goal of this work was to describe two MJD patients displaying the parkinsonian triad (tremor, bradykinesia and rigidity), namely on what concerns genetic variation in Parkinson's disease (PD) associated loci (PARK2, LRRK2, PINK1, DJ-1, SNCA, MAPT, APOE, and mtDNA tRNAGln T4336C). Patient 1 is a 40 year-old female (onset at 30 years of age), initially with a pure parkinsonian phenotype (similar to the phenotype previously reported for her mother). Patient 2 is a 38 year-old male (onset at 33 years of age), presenting an ataxic phenotype with parkinsonian features (not seen either in other affected siblings or in his father). Both patients presented an expanded ATXN3 allele with 72 CAG repeats. No PD mutations were found in the analyzed loci. However, allelic variants previously associated with PD were observed in DJ-1 and APOE genes, for both patients. The present report adds clinical and genetic information on this particular and rare MJD presentation, and raises the hypothesis that DJ-1 and APOE polymorphisms may confer susceptibility to the parkinsonian phenotype in MJD.