TY - JOUR
T1 - Genetic testing for Parkinson's disease in Israel
T2 - Insights from the Rostock Parkinson's Disease (ROPAD) study
AU - Anis, Saar
AU - Weill, Caroline
AU - Ponger, Penina
AU - Nassar, Maria
AU - Reiner, Johnathan
AU - Chorin, Odelia
AU - Parlar, Sitki Cem
AU - Alcalay, Roy N.
AU - Gan-Or, Ziv
AU - Ezra, Adi
AU - Saar, Adi
AU - Thaler, Avner
AU - Cohen, Oren S.
AU - Zlotnik, Yair
AU - Benizri, Sandra
AU - Nitsan, Zeev
AU - Djaldetti, Ruth
AU - Yahalom, Gilad
AU - Schlesinger, Ilana
AU - Klein, Christine
AU - Paul, Jefri J.
AU - Curado, Filipa
AU - Oren, Limor
AU - Iftikhar, Sana
AU - Bauer, Peter
AU - Gurevich, Tanya
AU - Arkadir, David
AU - Hassin-Baer, Sharon
AU - Greenbaum, Lior
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/8
Y1 - 2025/8
N2 - 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.
AB - 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.
KW - GBA1
KW - Genetic testing
KW - LRRK2
KW - PRKN
KW - Parkinson's disease
KW - ROPAD
UR - https://www.scopus.com/pages/publications/105009616434
U2 - 10.1016/j.parkreldis.2025.107940
DO - 10.1016/j.parkreldis.2025.107940
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C2 - 40617169
AN - SCOPUS:105009616434
SN - 1353-8020
VL - 137
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
M1 - 107940
ER -