Clinical and Genetic Analysis of Costa Rican Patients With Parkinson's Disease

Abstract

Background: Most research in genomics of Parkinson's disease (PD) has been done in subjects of European ancestry, leading to sampling bias and leaving Latin American populations underrepresented. We sought to clinically characterize PD patients of Costa Rican origin and to sequence familial PD and atypical parkinsonism-associated genes in cases and controls.Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, and motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes including GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, and ATP13A2.Results: Mean age of PD probands was 62.12 ± 13.51 years; 57.6% were male. The frequency of risk and protective factors averaged ~45%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders, and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants in LRRK2 were nominally associated with PD; six were located between amino acids p.1620 and 1623 in the C-terminal-of-ROC (COR) domain of Lrrk2. Non-synonymous GBA variants (p.T369M, p.N370S, and p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R.Discussion: This is the first study that describes sociodemographics, risk factors, clinical presentation, and genetics of Costa Rican patients with PD, adding information to genomics research in a Latino population.

Lack of full sequencing GBA1 studies for patients with Parkinson’s disease in Latin America

“…For example, we excluded the study from Costa Rica from the meta-analysis to reduce heterogeneity. The study found no GBA1 variants in patients with PD, probably due to low sample size, the method of sequencing (molecular inversion probes), and a geographical enrollment bias (participants from a specific metropolitan area, in the detriment of metropolitan areas and coastal zones of the country) 15 . Full sequencing of GBA1 in Latinos has already discovered the pathogenic p.K198E variant in Colombia, with a prevalence of 6% in patients with PD, increasing the disease risk six-fold 7 , showing that some variants of clinical relevance may only be reported after sequencing the whole gene.…”

The Landscape of Monogenic Parkinson’s Disease in Populations of Non-European Ancestry: A Narrative Review

“…Furthermore, according to this study, p.R1441G is rare in Latin America, even in patients of Spanish ancestry, as one case found, had a different haplotype possibly owing to mixed ancestry [30]. No known pathogenic LRRK2 mutations could be identified in a study assessing the Costa Rican PD population (Clinical and Genetic Analysis of Costa Rican PD population) [31].…”

“…Regarding Latin American populations, no SNCA pathogenic variants were reported in a study assessing the population of Costa Rica [31]. Moreover, in a cohort of 141 cases from families with apparently dominant PD inheritance in Brazil, no SNCA mutations could be identified [49].…”

Frequency of Hereditary and GBA1‐Related Parkinsonism in Latin America: A Systematic Review and Meta‐Analysis

“…This review assessed 3014 studies, of which 73 met the inclusion criteria 20,35–106 . The process detailing the step‐by‐step inclusion and exclusion criteria is summarized in the PRISMA flow diagram 107 shown in Figure S2.…”