2026-04-29T00:59:51Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/252082024-10-23T09:08:08Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Jesús, Silvia author Huertas, Ismael author Bernal-Bernal, Inmaculada author Bonilla-Toribio, Marta author Cáceres-Redondo, María Teresa author Vargas-González, Laura author Gómez-Llamas, Myriam author Carrillo, Fátima author Calderón, Enrique author Carballo, Manuel author Gómez-Garre, Pilar author Mir, Pablo 2024-10-23T09:08:08Z 2024-10-23T09:08:08Z 2016-12-28 http://hdl.handle.net/10668/10720 https://hdl.handle.net/20.500.12105/25208 28030538 10.1371/journal.pone.0167749 1932-6203 PloS one 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. eng GBA Variants Influence Motor and Non-Motor Features of Parkinson's Disease research article