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Originally published in Science Express on 21 November 2002
Science 10 January 2003:
Vol. 299. no. 5604, pp. 256 - 259
DOI: 10.1126/science.1077209
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Reports

Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism

Vincenzo Bonifati,12* Patrizia Rizzu,1 Marijke J. van Baren,1 Onno Schaap,1 Guido J. Breedveld,1 Elmar Krieger,3 Marieke C. J. Dekker,1 Ferdinando Squitieri,4 Pablo Ibanez,5 Marijke Joosse,1 Jeroen W. van Dongen,1 Nicola Vanacore,26 John C. van Swieten,7 Alexis Brice,5 Giuseppe Meco,2 Cornelia M. van Duijn,1 Ben A. Oostra,1 Peter Heutink1*

The DJ-1 gene encodes a ubiquitous, highly conserved protein. Here, we show that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism. The function of the DJ-1 protein remains unknown, but evidence suggests its involvement in the oxidative stress response. Our findings indicate that loss of DJ-1 function leads to neurodegeneration. Elucidating the physiological role of DJ-1 protein may promote understanding of the mechanisms of brain neuronal maintenance and pathogenesis of Parkinson's disease.

1 Genetic-Epidemiologic Unit, Department of Clinical Genetics, Department of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, Post Office Box 1738, 3000 DR Rotterdam, Netherlands.
2 Department of Neurological Sciences, "La Sapienza" University, Viale dell'Università 30, 00185 Rome, Italy.
3 Centre for Molecular and Biomolecular Informatics, University Medical Center Nijmegen, Geert Grooteplein Zuid 30, 6525 GA Nijmegen, Netherlands.
4 Neurogenetics Unit, IRCCS INM Neuromed, Località Camerelle, 86077 Pozzilli, Italy.
5 INSERM U 289, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.
6 Laboratory of Epidemiology and Biostatistics, National Institute for Health, 00161 Roma, Italy.
7 Department of Neurology, Erasmus Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, Netherlands.
*   To whom correspondence should be addressed. E-mail: bonifati{at}kgen.fgg.eur.nl or heutink{at}kgen.fgg.eur.nl

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PARK6-linked autosomal recessive early-onset parkinsonism in Asian populations.
Y. Hatano, K. Sato, B. Elibol, H. Yoshino, Y. Yamamura, V. Bonifati, H. Shinotoh, M. Asahina, S. Kobayashi, A. R. Ng, et al. (2004)
Neurology 63, 1482-1485
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