Drs. Duran and Mencacci made equal contributions.
The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease†
Version of Record online: 5 DEC 2012
Copyright © 2012 Movement Disorders Society
Volume 28, Issue 2, pages 232–236, February 2013
How to Cite
Duran, R., Mencacci, N. E., Angeli, A. V., Shoai, M., Deas, E., Houlden, H., Mehta, A., Hughes, D., Cox, T. M., Deegan, P., Schapira, A. H., Lees, A. J., Limousin, P., Jarman, P. R., Bhatia, K. P., Wood, N. W., Hardy, J. and Foltynie, T. (2013), The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease. Mov. Disord., 28: 232–236. doi: 10.1002/mds.25248
Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://olabout.wiley.com/WileyCDA/Section/id-817008.html
Funding agencies: R.D. received a postdoctoral fellowship from Alfonso Martin Escudero Foundation (Spain). J.H., N.W., and A.H.S. received research support from the UK Medical Research Council and Wellcome Trust. This work was supported by a Wellcome/MRC Parkinson's Disease Consortium grant to UCL/IoN, the University of Sheffield, and the MRC Protein Phosphorylation Unit at the University of Dundee (grant no.: WT089698). Funding to pay the Open Access publication charges for this article was provided by the Wellcome/MRC Parkinson's Disease Consortium grant to UCL/IoN, the University of Sheffield, and the MRC Protein Phosphorylation Unit at the University of Dundee. The clinical sample collection was supported by Parkinson's UK (K-0901; to T.F. and N.W.). Additional support came from the Reta Lila Trust (to A.J.L. and J.H.).
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue online: 23 FEB 2013
- Version of Record online: 5 DEC 2012
- Manuscript Accepted: 20 AUG 2012
- Manuscript Revised: 30 JUL 2012
- Manuscript Received: 25 MAY 2012
- Parkinson's disease;
- Gaucher's disease;
- early onset
Heterozygous loss-of-function mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the recessive lysosomal storage disorder, Gaucher's disease (GD), are the strongest known risk factor for Parkinson's disease (PD). Our aim was to assess the contribution of GBA1 mutations in a series of early-onset PD.
One hundred and eighty-five PD patients (with an onset age of ≤50) and 283 age-matched controls were screened for GBA1 mutations by Sanger sequencing.
We show that the frequency of GBA1 mutations is much higher in this patient series than in typical late-onset patient cohorts. Furthermore, our results reveal that the most prevalent PD-associated GBA1 mutation is E326K, a variant that does not, when homozygous, cause GD.
Our results confirm recent reports that the mutation, E326K, predisposes to PD and suggest that, in addition to reduced GBA1 activity, other molecular mechanisms may contribute to the development of the disease. © 2012 Movement Disorder Society