Clinical profiles associated with LRRK2 and GBA mutations in Brazilians with Parkinson's disease

• DOI: 10.1016/j.jns.2017.08.3249
• Publication Date: 2017-08-25T04:31:48Z
• Authors: Camilla P. da Silva; Gabriella de M. A...; Pedro H. Cabello ...; Mário Campos; João S. Pereira; Sarah R. de A. Ramos; Caroline M. Nasci...; Danielle D. Voigt; Ana Lucia Rosso; Marco A. Araujo L...; Luiz Felipe R. Va...; Denise H. Nicaretta; Marcus V. Della C...; Delson José da Silva; Andressa P. Gonça...; Jussara M. dos Sa...; Veluma Calassara; Débora Cristina T...; Cyro J. de M. Mar...; Cíntia B. Santos-...; Márcia M.G. Pimentel
• Keywords: Adult; Aged, 80 and over; Male; Heterozygote; Parkinson Disease; Middle Aged; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; 3. Good health; Cohort Studies; Young Adult; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Mutation; Glucosylceramidase; Humans; Female; Brazil; Genetic Association Studies; Aged

Parkinson's disease (PD) is a neurodegenerative disorder characterized by remarkable phenotypic variability. Accumulated evidence points that the manifestation of PD clinical signs might be differentially modified by genetic factors, as mutations in LRRK2 and GBA genes. In this sense, the clarification of the genotype-phenotype correlations in PD has important implications in predicting prognosis and can contribute to the development of specific therapeutic approaches.Here, we conducted the first comparative analysis of motor and non-motor features in 17 LRRK2 and 22 GBA mutation carriers and 93 non-carriers unrelated PD patients from Brazil, a highly admixed population.Significant differences were found between the three groups. LRRK2 PD patients presented more occurrence of familiar history. Resting tremor was observed in a lower frequency in GBA mutation carries. In contrast, gait freezing and dysautonomia was present in lower frequencies in LRRK2 carriers. Besides that, LRRK2 and GBA mutation carriers showed a higher incidence of depressive symptoms and a younger age at onset, when compared to non-carriers.Our results suggest that specific mutations in GBA and LRRK2 influence the clinical signs of the disease, with significant implications for handling of specific patient groups.