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Open Access Case report

Parkinsonian phenotype in Machado-Joseph disease (MJD/SCA3): a two-case report

Conceição Bettencourt1234*, Cristina Santos5, Paula Coutinho36, Patrizia Rizzu7, João Vasconcelos8, Teresa Kay9, Teresa Cymbron123, Mafalda Raposo12, Peter Heutink7 and Manuela Lima123

Author Affiliations

1 Center of Research in Natural Resources (CIRN), University of the Azores, Ponta Delgada, Portugal

2 Department of Biology, University of the Azores, Ponta Delgada, Portugal

3 Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal

4 Laboratorio de Biología Molecular, Instituto de Enfermedades Neurológicas, Fundación Socio-Sanitaria de Castilla-La Mancha, Guadalajara, Spain

5 Unitat Antropologia Biològica, Dep. Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain

6 Department of Neurology, Hospital São Sebastião, Feira, Portugal

7 Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands

8 Department of Neurology, Hospital of Divino Espirito Santo, Ponta Delgada, Portugal

9 Department of Clinical Genetics, Hospital of D. Estefania, Lisbon, Portugal

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BMC Neurology 2011, 11:131  doi:10.1186/1471-2377-11-131

Published: 24 October 2011

Abstract

Background

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).

Case presentation

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.

Conclusions

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.