Nurit Omer1,2, Nir Giladi1,2,3, Tanya Gurevich1,2,3, Anat Bar-Shira4, Mali Gana-Weisz5, Orly Goldstein5, Meir Kestenbaum2,6, Jesse M Cedarbaum7,8, Avi Orr-Urtreger2,5, Anat Mirelman2,3,9, Avner Thaler1,2,3,9. 1. Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel. 2. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 3. Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel. 4. Genetic Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel. 5. Genomic Research Laboratory for Neurodegeneration, Tel-Aviv Medical Center, Tel-Aviv, Israel. 6. Neurology Department, Meir Hospital, Kfar-Saba, Israel. 7. Biogen Inc, Cambridge, Massachusetts, USA. 8. Coeruleus Clinical Sciences LLC, Woodbridge, Connecticut, USA. 9. Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel.
Abstract
BACKGROUND: The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2-PD and more severe among patients with GBA-PD; however, whether an additive phenotypical effect occurs among dual-mutation carriers requires validation. OBJECTIVE: The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single-mutation presentation. METHODS: Patients with PD were genotyped for the G2019S-LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA-PD, severe GBA-PD, LRRK2-PD, and LRRK2+GBA-PD. Clinical symptoms were evaluated using performance-based measures. RESULTS: A total of 1090 patients with idiopathic PD, 155 patients with LRRK2-PD, 155 patients with mild GBA-PD, 56 patients with severe GBA-PD, and 27 patients with LRRK2+GBA-PD participated in this study. The patients with LRRK2-PD and LRRK2+GBA-PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P < 0.01) and better olfaction (P < 0.01) compared with GBA-PD. CONCLUSIONS: Patients with LRRK2+GBA-PD were symptomatically similar to patients with LRRK2-PD, suggesting a dominant effect of LRRK2 over GBA in the phenotypic presentation.
BACKGROUND: The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2-PD and more severe among patients with GBA-PD; however, whether an additive phenotypical effect occurs among dual-mutation carriers requires validation. OBJECTIVE: The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single-mutation presentation. METHODS: Patients with PD were genotyped for the G2019S-LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA-PD, severe GBA-PD, LRRK2-PD, and LRRK2+GBA-PD. Clinical symptoms were evaluated using performance-based measures. RESULTS: A total of 1090 patients with idiopathic PD, 155 patients with LRRK2-PD, 155 patients with mild GBA-PD, 56 patients with severe GBA-PD, and 27 patients with LRRK2+GBA-PD participated in this study. The patients with LRRK2-PD and LRRK2+GBA-PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P < 0.01) and better olfaction (P < 0.01) compared with GBA-PD. CONCLUSIONS: Patients with LRRK2+GBA-PD were symptomatically similar to patients with LRRK2-PD, suggesting a dominant effect of LRRK2 over GBA in the phenotypic presentation.
Authors: Maria Kedariti; Emanuele Frattini; Pascale Baden; Susanna Cogo; Laura Civiero; Elena Ziviani; Gianluca Zilio; Federico Bertoli; Massimo Aureli; Alice Kaganovich; Mark R Cookson; Leonidas Stefanis; Matthew Surface; Michela Deleidi; Alessio Di Fonzo; Roy N Alcalay; Hardy Rideout; Elisa Greggio; Nicoletta Plotegher Journal: NPJ Parkinsons Dis Date: 2022-07-19
Authors: Nurit Omer; Nir Giladi; Tanya Gurevich; Anat Bar-Shira; Mali Gana-Weisz; Tal Glinka; Orly Goldstein; Meir Kestenbaum; Jesse M Cedarbaum; Omar S Mabrouk; Kyle B Fraser; Julia C Shirvan; Avi Orr-Urtreger; Anat Mirelman; Avner Thaler Journal: Mov Disord Date: 2021-09-22 Impact factor: 9.698
Authors: Yuri L Sosero; Eric Yu; Lynne Krohn; Uladzislau Rudakou; Kheireddin Mufti; Jennifer A Ruskey; Farnaz Asayesh; Sandra B Laurent; Dan Spiegelman; Stanley Fahn; Cheryl Waters; S Pablo Sardi; Sara Bandres-Ciga; Roy N Alcalay; Ziv Gan-Or; Konstantin Senkevich Journal: Neurobiol Aging Date: 2021-02-28 Impact factor: 5.133
Authors: Roberto A Ortega; Cuiling Wang; Deborah Raymond; Nicole Bryant; Clemens R Scherzer; Avner Thaler; Roy N Alcalay; Andrew B West; Anat Mirelman; Yuliya Kuras; Karen S Marder; Nir Giladi; Laurie J Ozelius; Susan B Bressman; Rachel Saunders-Pullman Journal: JAMA Netw Open Date: 2021-04-01