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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 2016; 629:160-164NL

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.

Authors+Show Affiliations

Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, Antwerp University Hospital, Edegem, Belgium. Electronic address: david.crosiers@uza.be.Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, Hospital Network Antwerp, Middelheim, Antwerp, Belgium.Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, Hospital Network Antwerp, Middelheim, Antwerp, Belgium.Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, Antwerp University Hospital, Edegem, Belgium.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27397011

Citation

Crosiers, David, et al. "Mutations in Glucocerebrosidase Are a Major Genetic Risk Factor for Parkinson's Disease and Increase Susceptibility to Dementia in a Flanders-Belgian Cohort." Neuroscience Letters, vol. 629, 2016, pp. 160-164.
Crosiers D, Verstraeten A, Wauters E, et al. 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. 2016;629:160-164.
Crosiers, D., Verstraeten, A., Wauters, E., Engelborghs, S., Peeters, K., Mattheijssens, M., ... Cras, P. (2016). Mutations in glucocerebrosidase are a major genetic risk factor for Parkinson's disease and increase susceptibility to dementia in a Flanders-Belgian cohort. Neuroscience Letters, 629, pp. 160-164. doi:10.1016/j.neulet.2016.07.008.
Crosiers D, et al. 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. 2016 08 26;629:160-164. PubMed PMID: 27397011.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations in glucocerebrosidase are a major genetic risk factor for Parkinson's disease and increase susceptibility to dementia in a Flanders-Belgian cohort. AU - Crosiers,David, AU - Verstraeten,Aline, AU - Wauters,Eline, AU - Engelborghs,Sebastiaan, AU - Peeters,Karin, AU - Mattheijssens,Maria, AU - De Deyn,Peter P, AU - Theuns,Jessie, AU - Van Broeckhoven,Christine, AU - Cras,Patrick, Y1 - 2016/07/07/ PY - 2016/05/10/received PY - 2016/07/04/revised PY - 2016/07/06/accepted PY - 2016/7/12/entrez PY - 2016/7/12/pubmed PY - 2017/7/27/medline KW - GBA KW - Genotype-phenotype correlation KW - Glucocerebrosidase KW - Parkinson’s disease SP - 160 EP - 164 JF - Neuroscience letters JO - Neurosci. Lett. VL - 629 N2 - 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. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/27397011/Mutations_in_glucocerebrosidase_are_a_major_genetic_risk_factor_for_Parkinson's_disease_and_increase_susceptibility_to_dementia_in_a_Flanders_Belgian_cohort_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(16)30494-3 DB - PRIME DP - Unbound Medicine ER -