好色先生

好色先生

Explore the latest content from across our publications

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Association between glucocerebrosidase mutations and Parkinson’s disease in Ireland
Movement Disorders
S53 - Movement Disorders: Genetics and Clinical Features (3:52 PM-4:03 PM)
003

Genetic and environmental factors have been proposed to influence the etiology of Parkinson’s disease (PD). A number of susceptibility genes were identified; however the exact patomechanism remains elusive. Mutations in glucocerebrosidase (GBA) gene cause Gaucher’s disease (GD) by altering glucocerebrosidase activity. GBA mutations have been reported to be the most common genetic risk factor for PD (risk increased 2-30 times depending on ethnicity). Previous studies elsewhere had major flaws by restricting analysis to the most common mutations/ignoring intronic regions. The frequency of GBA mutations in PD patients has never been examined in the Irish population. 

To investigate for the first time in Ireland the prevalence and role of GBA in Parkinson's disease.

We prospectively recruited 314 Irish patients attending The Dublin Neurological Institute, Ireland and compared them to healthy controls. Comprehensive clinical assessment was performed. Full GBA gene sequencing analysis including inronic regions was performed in the Dept. of Neuroscience, Mayo Clinic, Jacksonville, FL.

The GBA carrier frequency was 6.7% in PD, 2.4% in controls and carrier status was associated with 3-fold increased PD risk. We identified a number of potentially pathogenic mutations including a p.G195E substitution and a p.G377C variant. The p.G377C variant was described in one case study of Gaucher’s disease from Northern Ireland as a compound heterozygote, but not in PD. Both variants will be discussed in detail. On genotype-phenotype assessment hallucinations, dyskinesia and dystonia were more prevalent in GBA-PD. 

The examination of the GBA in the Irish PD is novel. The genetic etiology of PD in Ireland differs from the continental Europe as seen (previous study) with the lower LRRK2 and higher than in most European countries GBA mutation frequency. Determining the genetic risk factors and prevalence of mutations in PD associated genes in different populations is critical to develop personalized  therapeutic approach.
Authors/Disclosures
Diana Angelika Olszewska, MD, PhD (Cork University Hospital)
PRESENTER
Dr. Olszewska has nothing to disclose.
Allan McCarthy, MD (Tallaght Hospital) No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Brian Magennis (Mater Hospital) No disclosure on file
Orla Hardiman, MD, FRCPI, FAAN (Trinity Biomedical Sciences Institute) Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Pharmaceuticals. Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cytokinetics . Dr. Hardiman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hardiman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Taylor and Francis. The institution of Dr. Hardiman has received research support from Science Foundation Ireland. The institution of Dr. Hardiman has received research support from HRB.
Owen A. Ross, PhD (Mayo Clinic Jacksonville) Dr. Ross has nothing to disclose.
Timothy Lynch, MD (Dublin Neurological Institute,) Dr. Lynch has nothing to disclose.