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Title
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Mutations in glucocerebrosidase are a major genetic risk factor for Parkinsons disease and increase susceptibility to dementia in a Flanders-Belgian cohort
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Author
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Abstract
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| Objective: To investigate the frequency of glucocerebrosidase (GBA) mutations in a Flanders-Belgian Parkinson's disease (PD) patient cohort and to assess genotype-phenotype correlations. Methods: We performed an in-depth sequencing of all coding exons of GBA in 266 clinically well characterized PD patients and 536 healthy control individuals. Results: We identified rare, heterozygous GBA mutations in 12 PD patients (4.5%) and in 2 healthy control individuals (0.37%), confirming the genetic association of GBA mutations with PD in the Flanders-Belgian population (p < 0.001). The patient carriers had a more severe Unified Parkinson's Disease Rating Scale (UPDRS) motor score than non-carriers. Also, GBA mutation status was a significant, independent predictor for the presence of dementia (OR = 12.43, 95% CI: 2.27-68.14. p = 0.004). Genetic association of PD with the common p.E326K and p.T369M variants in GBA was absent. Conclusion: In our Flanders-Belgian cohort, carrier status of a heterozygous GBA mutation was a strong genetic risk factor for PD. The GBA mutation frequency of 4.5% is comparable to previously reported data in other European PD patient cohorts. Furthermore, our clinical data suggest a more severe motor phenotype and a strong predisposition to dementia in GBA mutation carriers. (C) 2016 Elsevier Ireland Ltd. All rights reserved. |
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Language
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English
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Source (journal)
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Neuroscience letters. - Amsterdam
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Publication
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Amsterdam
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2016
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ISSN
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0304-3940
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DOI
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10.1016/J.NEULET.2016.07.008
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Volume/pages
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629
(2016)
, p. 160-164
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ISI
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000382409000029
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Pubmed ID
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27397011
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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