RT Journal Article
T1 GBA Variants Influence Motor and Non-Motor Features of Parkinson's Disease.
A1 Jesús, Silvia
A1 Huertas, Ismael
A1 Bernal-Bernal, Inmaculada
A1 Bonilla-Toribio, Marta
A1 Cáceres-Redondo, María Teresa
A1 Vargas-González, Laura
A1 Gómez-Llamas, Myriam
A1 Carrillo, Fátima
A1 Calderón, Enrique
A1 Carballo, Manuel
A1 Gómez-Garre, Pilar
A1 Mir, Pablo
AB The presence of mutations in glucocerebrosidase (GBA) gene is a known factor increasing the risk of developing Parkinson's disease (PD). Mutations carriers have earlier disease onset and are more likely to develop neuropsychiatric symptoms than other sporadic PD cases. These symptoms have primarily been observed in Parkinson's patients carrying the most common pathogenic mutations L444P and N370S. However, recent findings suggest that other variants across the gene may have a different impact on the phenotype as well as on the disease progression. We aimed to explore the influence of variants across GBA gene on the clinical features and treatment related complications in PD. In this study, we screened the GBA gene in a cohort of 532 well-characterised PD patients and 542 controls from southern Spain. The potential pathogeniticy of the identified variants was assessed using in-silico analysis and subsequently classified as benign or deleterious. As a result, we observed a higher frequency of GBA variants in PD patients (12.2% vs. 7.9% in controls, p = 0.021), earlier mean age at disease onset in GBA variant carriers (50.6 vs. 56.6 years; p = 0.013), as well as more prevalent motor and non-motor symptoms in patients carrying deleterious variants. In addition, we found that dopaminergic motor complications are influenced by both benign and deleterious variants. Our results highlight the fact that the impact on the phenotype highly depends on the potential pathogenicity of the carried variants. Therefore, the course of motor and non-motor symptoms as well as treatment-related motor complications could be influenced by GBA variants.
YR 2016
FD 2016-12-28
LK http://hdl.handle.net/10668/10720
UL http://hdl.handle.net/10668/10720
LA en
DS RISalud
RD Apr 10, 2025