Background: We examined the yield of a large-scale genetic testing for patients with Parkinson's disease (PD) in Israel, where risk factor variants in GBA1 and/or the pathogenic p.Gly2019Ser variant in LRRK2 are prevalent among the Ashkenazi Jewish population.
Methods: This study included data from all Israeli movement disorder clinics participating in the Rostock Parkinson's Disease (ROPAD) study. Patients were tested for variants in eight PD-related genes and 37 genes with possible phenotypic overlap.
Results: The sample consisted of 2699 PD patients recruited in three phases (1702 [63.1 %] males, mean age at onset 59.2 ± 10.6 years, 718 [26.6 %] with a family history of PD). Positive PD-relevant genetic test (PDGT) results were obtained in 512 participants (19.0 %). Among 187 (6.9 %) patients the results were due to pathogenic variants only in LRRK2, in 283 (10.5 %) due to risk factor variants only in GBA1, and another 15 patients (0.6 %) were carriers of variants in both genes. Twenty-six subjects (1.0 %) had a positive PDGT based on findings in PRKN (n = 19), PINK1 (n = 4), PARK7, SNCA, or VPS35 (one in each gene), and an additional patient had dual findings (GBA1 and SNCA). The most prevalent variants were LRRK2 p.Gly2019Ser and GBA1 p.Asn409Ser, detected in 191 (7.1 %) and 173 (6.4 %) patients, respectively. Excluding patients harboring only LRRK2 and/or GBA1 variants, the yield was 27/2214 (1.2 %). Seven participants, including one with a positive PDGT, had positive testing findings in genes related to dystonia (GCH1 and TOR1A) and dementia (MAPT).
Conclusions: Genetic testing for Israeli PD patients is beneficial, while the yield is primarily attributed to LRRK2 and GBA1 variants.
Keywords: GBA1; Genetic testing; LRRK2; PRKN; Parkinson's disease; ROPAD.
Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.