Clinical and genetic analysis of Costa Rican patients with Parkinson’s disease

Abstract

Background: Parkinson's disease (PD) involves environmental risk and protective factors as well as genetic variance. Most of the research in genomics has been done in subjects of European ancestry leading to sampling bias and leaving Latin American populations underrepresented. Objective: We sought to phenotype and genotype Costa Rican PD cases and controls. Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, 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, ATP13A2. Results: Mean age of PD probands was 62.12 ± 13.51 years, 57.6% were male. Prevalence of risk and protective factors reached 30%. 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.1620-1623 in the C-terminal-of-ROC (COR) domain of LRRK2. Nonsynonymous GBA variants (p.T369M, p.N370S, p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R. Conclusion: This is the first study that reports on sociodemographic, risk factors, clinical presentation and genetics of Costa Rican patients with PD.

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.…”

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

“…We thank Jennifer Ruskey, Sandra Laurent, Lynne Krohn, Uladzislau Rudakou, D. Rochefort, H. Catoire, V. Zaharieva, and Dr. Ellen Sylvie Sánchez-Más for their assistance. This article has already been published as preprint under medRxiv server ( 105 ).…”