title: GBA Variants Influence Motor and Non-Motor Features of Parkinson's Disease.
abstract: 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.
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Jesús
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: Huertas
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Bernal-Bernal
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bonilla-Toribio
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Cáceres-Redondo
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Vargas-González
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gómez-Llamas
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Carrillo
authors.affiliation: Servicio de Medicina Interna, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.|Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Calderón
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Carballo
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Gómez-Garre
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Mir
mesh_terms: D000368:Aged; D003071:Cognition; D020820:Dyskinesias / Q000150:complications; D005091:Exons / Q000235:genetics; D005260:Female; D005962:Glucosylceramidase / Q000235:genetics*; D006212:Hallucinations / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000235:genetics*; D015999:Multivariate Analysis; D009154:Mutation; D010300:Parkinson Disease / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D005962:Glucosylceramidase