The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease

Raquel Duran, Niccolo E. Mencacci, Aikaterini V. Angeli, Maryam Shoai, Emma Deas, Henry Houlden, Atul Mehta, Derralynn Hughes, Timothy M. Cox, Patrick Deegan, Anthony H. Schapira, Andrew J. Lees, Patricia Limousin, Paul R. Jarman, Kailash P. Bhatia, Nicholas W. Wood, John Hardy*, Tom Foltynie

*Corresponding author for this work

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)232-236
Number of pages5
JournalMovement Disorders
Volume28
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • E326K
  • Early onset
  • GBA
  • Gaucher's disease
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    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., & Foltynie, T. (2013). The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease. Movement Disorders, 28(2), 232-236. https://doi.org/10.1002/mds.25248