Association Between Glucocerebrosidase Mutations and Parkinson's Disease in Ireland
Multiple studies implicate heterozygous GBA mutations as a major genetic risk factor for Parkinson's disease (PD); however, the frequency of mutations has never been examined in PD patients from the Irish population. We prospectively recruited 314 unrelated Irish PD patients (UK Brain Bank Crit...
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doaj-7649c3497e7b4ebc8475d06bcb0c7e702020-11-25T03:17:17ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-06-011110.3389/fneur.2020.00527531718Association Between Glucocerebrosidase Mutations and Parkinson's Disease in IrelandDiana A. Olszewska0Diana A. Olszewska1Diana A. Olszewska2Allan McCarthy3Allan McCarthy4Alexandra I. Soto-Beasley5Ronald L. Walton6Brian Magennis7Russell L. McLaughlin8Orla Hardiman9Orla Hardiman10Owen A. Ross11Owen A. Ross12Owen A. Ross13Tim Lynch14Tim Lynch15The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, IrelandDepartment of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, United StatesSchool of Medicine and Medical Science, University College Dublin, Dublin, IrelandThe Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, IrelandDepartment of Neurology, The Adelaide and Meath Hospital, Dublin, IrelandDepartment of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, United StatesDepartment of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, United StatesThe Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, IrelandTrinity College Dublin, Smurfit Institute of Genetics, Dublin, IrelandDepartment of Neurology, Beaumont Hospital, Dublin, IrelandAcademic Unit of Neurology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, IrelandDepartment of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, United StatesSchool of Medicine and Medical Science, University College Dublin, Dublin, IrelandDepartment of Clinical Genomics, Mayo Clinic, Jacksonville, FL, United StatesThe Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, IrelandSchool of Medicine and Medical Science, University College Dublin, Dublin, IrelandMultiple studies implicate heterozygous GBA mutations as a major genetic risk factor for Parkinson's disease (PD); however, the frequency of mutations has never been examined in PD patients from the Irish population. We prospectively recruited 314 unrelated Irish PD patients (UK Brain Bank Criteria) and 96 Irish healthy controls (without any signs or family history of parkinsonism) attending. The Dublin Neurological Institute (DNI). Complete exon GBA Sanger sequencing analysis with flanking intronic regions was performed. The GBA carrier frequency was 8.3% in PD and 3.1% in controls. We identified a number of potentially pathogenic mutations including a p.G195E substitution and a p.G377C variant, previously described in a case study of Gaucher's disease in Ireland. On genotype–phenotype assessment hallucinations, dyskinesia, and dystonia were more prevalent in GBA-PD. The genetic etiology of PD in Ireland differs from the continental Europe as seen with the lower LRRK2 and higher than in most European countries GBA mutation frequency. Determining genetic risk factors in different ethnicities will be critical for future personalized therapeutic approach.https://www.frontiersin.org/article/10.3389/fneur.2020.00527/fullGBAglucocerebrosidaseIrelandsequencingParkinson's disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Diana A. Olszewska Diana A. Olszewska Diana A. Olszewska Allan McCarthy Allan McCarthy Alexandra I. Soto-Beasley Ronald L. Walton Brian Magennis Russell L. McLaughlin Orla Hardiman Orla Hardiman Owen A. Ross Owen A. Ross Owen A. Ross Tim Lynch Tim Lynch |
spellingShingle |
Diana A. Olszewska Diana A. Olszewska Diana A. Olszewska Allan McCarthy Allan McCarthy Alexandra I. Soto-Beasley Ronald L. Walton Brian Magennis Russell L. McLaughlin Orla Hardiman Orla Hardiman Owen A. Ross Owen A. Ross Owen A. Ross Tim Lynch Tim Lynch Association Between Glucocerebrosidase Mutations and Parkinson's Disease in Ireland Frontiers in Neurology GBA glucocerebrosidase Ireland sequencing Parkinson's disease |
author_facet |
Diana A. Olszewska Diana A. Olszewska Diana A. Olszewska Allan McCarthy Allan McCarthy Alexandra I. Soto-Beasley Ronald L. Walton Brian Magennis Russell L. McLaughlin Orla Hardiman Orla Hardiman Owen A. Ross Owen A. Ross Owen A. Ross Tim Lynch Tim Lynch |
author_sort |
Diana A. Olszewska |
title |
Association Between Glucocerebrosidase Mutations and Parkinson's Disease in Ireland |
title_short |
Association Between Glucocerebrosidase Mutations and Parkinson's Disease in Ireland |
title_full |
Association Between Glucocerebrosidase Mutations and Parkinson's Disease in Ireland |
title_fullStr |
Association Between Glucocerebrosidase Mutations and Parkinson's Disease in Ireland |
title_full_unstemmed |
Association Between Glucocerebrosidase Mutations and Parkinson's Disease in Ireland |
title_sort |
association between glucocerebrosidase mutations and parkinson's disease in ireland |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2020-06-01 |
description |
Multiple studies implicate heterozygous GBA mutations as a major genetic risk factor for Parkinson's disease (PD); however, the frequency of mutations has never been examined in PD patients from the Irish population. We prospectively recruited 314 unrelated Irish PD patients (UK Brain Bank Criteria) and 96 Irish healthy controls (without any signs or family history of parkinsonism) attending. The Dublin Neurological Institute (DNI). Complete exon GBA Sanger sequencing analysis with flanking intronic regions was performed. The GBA carrier frequency was 8.3% in PD and 3.1% in controls. We identified a number of potentially pathogenic mutations including a p.G195E substitution and a p.G377C variant, previously described in a case study of Gaucher's disease in Ireland. On genotype–phenotype assessment hallucinations, dyskinesia, and dystonia were more prevalent in GBA-PD. The genetic etiology of PD in Ireland differs from the continental Europe as seen with the lower LRRK2 and higher than in most European countries GBA mutation frequency. Determining genetic risk factors in different ethnicities will be critical for future personalized therapeutic approach. |
topic |
GBA glucocerebrosidase Ireland sequencing Parkinson's disease |
url |
https://www.frontiersin.org/article/10.3389/fneur.2020.00527/full |
work_keys_str_mv |
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