DJ-1 Mutations are Rare in a Swedish Parkinson Cohort



Anna Anvret 1, Jeff G Blackinton 1, 2, Marie Westerlund 1, Caroline Ran 1, Olof Sydow 3, Thomas Willows 3, Anna Håkansson 4, Hans Nissbrandt 4, Andrea Carmine Belin*, 1
1 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
2 Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA
3 Department of Neurology, Karolinska University Hospital, Stockholm, Sweden
4 Department of Pharmacology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden


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© Anvret et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Neuroscience, Retzius väg 8, B2:4, Karolinska Institutet, 171 77 Stockholm, Sweden; Tel: +46-8-524 870 51; Fax: +46-8-323 742; E-mail: andrea.carmine.belin@ki.se


Abstract

Mutations in the PARK7 gene, DJ-1, have been reported to cause early-onset and familial Parkinson’s disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for the maintenance of mitochondria. We have screened three coding regions of DJ-1 (exon 2, 5 and 7) in a Swedish Parkinson cohort. The Swedish PD material consisted of 67 patients with a self reported positive family history of PD and 77 patients with early-onset of disease (≤50 years old). We detected two patients with the previously reported synonymous mutation, Ala167Ala (c.501A>G, rs71653621), in exon 7. No Ala167Ala carriers were identified among 213 neurologically healthy Swedish controls. Mechanisms by which the synonymous Ala167Ala mutation can have consequences are unknown. It may affect the mRNA stability, secondary structure of mRNA, synthesis, turnover, protein folding and function. We could show a 1.3% decrease in DJ-1 mRNA folding energy in the A<G substituted sequence compared to the wild type sequence in silico, suggesting a possible small effect of Ala167Ala on DJ-1 gene function. This is the first report on an identified DJ-1 mutation in Swedish PD patients. Our results, in combination with those of previous studies, strengthen the hypothesis that alterations in DJ-1 are not a common cause of familial and early-onset PD world-wide.

Keywords: PARK7, mitochondria, mutation, oxidative stress.