Análise fenotípica comparativa em pacientes brasileiros com doença de Parkinson com e sem mutações nos genes LRRK2 e GBA

Abstract

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. The objective of this study was to conduct a comparative analysis of motor and non-motor features in LRRK2 and GBA mutations carriers and non-carriers in a cohort of Brazilian PD patients. Molecular analyzes to identify the variants were performed through the sequencing of polymerase chain reaction products. For compilation of clinical and demographic data of 131 patients with PD, a form was elaborated, contemplating the presence or absence of motor and non-motor symptoms, as well as the response to treatment with levodopa, age at onset and family history of the disease. Comparison of data from 22 probands with GBA mutations, 17 individuals with LRRK2 G2019S and 96 idiopathic PD patients showed significant differences among the three groups regarding the age at onset (p = 0.004), family history of the disease (p = 0.003) and the presence of rest tremor (p = 0.03); motor complications, as gait freezing (p = 0.0498), and non-motor complications, as depressive symptoms (p = 0.04) and dysautonomia (p <0.0001). Age at onset of mutation carriers resulted in a lower mean than the age of non-carriers, suggesting that the presence of mutations may advance the disease onset. Resting tremor was in lower frequency in GBA-PD than in the other groups. In LRRK2-PD, patients showed a lower incidence of gait freezing and dysautonomia when compared to GBA-PD and IPD. In addition, a lower proportion of depressive symptoms was identified in both mutation groups compared to idiopathic PD probands. These clinical data reveal differences in the disease evolution and suggest the existence of different genetic subtypes. Our observations corroborate the hypothesis that the clinical presentation of the disease can be modified by LRRK2 and GBA mutations. Similarities in PD phenotypes among patients with comparable genotypes may benefit the elucidation of clinical profiles according to genetic characteristics.