Objective: This study aims to describe the genetic and clinical profile of 32 subjects with familial PD using NGS genetic panel and eMotion software system to gait assessment in a population sample from Colombian Southwest.

Background: Familial forms of Parkinson’s disease account for 5%-15% of cases. Highly-penetrant rare genetic alterations in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1 and GBA genes have been linked with familial PD and common genetic variability at 90 loci have been linked to risk for PD in European and Asian populations mainly. Little is known about the Latin-American community. Strategies to asses PD are focused on biomarkers with only one reported research based on the use of technology to measure gait abnormalities in healthy carriers of the LRRK2 variant.

Method: 32 subjects from 11 families were evaluated (18 PD patients). MDS-UPDRS III and MoCA tests were applied. We obtained Arm Swing Asymmetry (ASA) and global speed with eMotion System Kinect. Genetic analysis was conducted from DNA obtained of blood samples and were analyzed using a customized NGS neurodegenerative panel. Variant impact was established according to reports in population and genetic databases and bioinformatics prediction tools. Descriptive analysis was performed continuous data were reported as the mean and SD.

Results: 13 PD patients (70%) were males with a median age of 72 (SD7.36). Age of onset was 61.1 (SD7.68), 60% has an early stage. MDS-UPDRS III= 36.5 (SD19.2). 70% were PIDG subtype. Moca Test score was 20.9 (SD4.86). 9 PD cases and 1 healthy relative had an abnormal ASA detected by Kinect assessment. Lower speed was found in subjects with VPS13C, GCH1, SYNJ1, GBA, TH and/or LRRK2. In 12 PD patients (66%) and 6 healthy relatives (42.8%) were identified at least one genetic variant. Nine novel heterozygous deleterious variants were identified in GCH1, SYNJ1, PINK1, GBA, TH, and LRRK2 genes. Uncertain significance variants were reported in six genes.

Conclusion: Identifying the remaining genetic risk across different ancestral groups is a critical step to precision medicine for PD. We found that the abnormalities of gait variables (lower limbs speed and ASA) may be related with the deleterious variants. We suggest that PD genetic analysis should be complement with gait measurements technology-based.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-genetic-profile-of-familial-parkinsons-disease-in-cali-colombia/