Mutations in glucocerebrosidase are a major genetic risk factor for Parkinson's disease and increase susceptibility to dementia in a Flanders-Belgian cohort.
Neurosci Lett
; 629: 160-164, 2016 08 26.
Article
em En
| MEDLINE
| ID: mdl-27397011
ABSTRACT
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Predisposição Genética para Doença
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Demência
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Glucosilceramidase
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article