Session Information
Date: Monday, October 8, 2018
Session Title: Parkinson's Disease: Genetics
Session Time: 1:15pm-2:45pm
Location: Hall 3FG
Objective: To study differences in disease characteristics in PD associated with 1 or 2 mutations in the most common PD-associated genes in the Ashkenazi Jewish (AJ) population, GBA and LRRK2.
Background: About 30% of patients with sporadic PD and more than 40% of patients with familial PD of AJ descent carry the LRRK2 p.G2019S mutation, a GBA mutation, or both.
Methods: GBA and LRRK2 were fully sequenced using DNA samples of AJ PD patients (n=566) attending the Movement Disorders Institute between 2008 and 2017.4 study populations were compared regarding age at symptom onset (AAO) and clinical characteristics obtained from patient files: patients with a GBA mutation negative for the LRRK2 G2019S mutation (GBA+/LRRK2-), patients with the G2019S mutation but negative for GBA mutations (GBA-/LRRK2+), patients with both (GBA+/LRRK2+) and patients with neither mutation (GBA-/LRRK2-). Comparisons among the groups was performed by non-parametric Kruskal-Wallis and chi-square tests.
Results: 11 GBA+/LRRK2+carriers (36.4% males, AAO 53.9±10.9 years), 64 GBA-/LRRK2+ carriers (57.8% males, AAO 57.9±10.9 years), 67 GBA+/LRRK2- carriers (61.2% males, AAO 57.7±11.0 years), and 81 GBA-/LRRK2- PD patients (selected using a random list generator, 66.7% males, AAO 61.8±11.8 years) were identified. AAO was significantly younger for the double mutation group (p=0.02). PD duration at last follow up was similar among the 4 groups (p=0.35). Levodopa-induced dyskinesia was most common for GBA+/LRRK2+ PD group (73%), followed by GBA-/LRRK2+ carriers (62%), GBA+/LRRK2- carriers (53%) and GBA-/LRRK2- (32%, p=0.001). A significantly higher proportion of patients with GBA+/LRRK2- had dementia, RBD and psychosis (37%, 49%, 48%) comparing to the other groups, GBA-/LRRK2+ (6%, 17%, 17%), GBA+/LRRK2+ (9%, o%, 9%) and GBA-/LRRK2- (14%, 33%, 18%), (p≤0.001). Prevalence of FOG and time from onset to H & Y 3 did not differ significantly among groups.
Conclusions: In this retrospective cross sectional study of AJ PD patients, differences in disease course were found between mutation groups reflecting genotype-phenotype impact. GBA mutation was associated with more prevalent non-motor/neuropsychiatric symptoms. Patients carrying both a GBA mutation and LRRK2 mutation exhibited the youngest age of onset but less neuropsychiatric complications, similar to LRRK2 mutation carriers without GBA mutations, probably suggesting differential distribution of neurodegeneration.
To cite this abstract in AMA style:
V. Livneh, G. Yahalom, L. Greenbaum, S. Israeli-Korn, T. Fay-Karmon, S. Hassin, Z. Gan Or. PD associated with GBA and LRRK2 mutations: Genotype-phenotype correlation [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/pd-associated-with-gba-and-lrrk2-mutations-genotype-phenotype-correlation/. Accessed October 7, 2024.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/pd-associated-with-gba-and-lrrk2-mutations-genotype-phenotype-correlation/