Screening for PRKN and PINK1 mutations in Ecuadorian patients with early-onset Parkinson's Disease.

Introduction: Early-onset Parkinson's Disease (EOPD) is a neurodegenerative disease with the clinical manifestation of movement symptoms before the age of 50. Patients with EOPD frequently have a positive family history of disease, with bi-allelic loss of function mutations in PRKN and PINK1 as the most common genetic cause. To date, the majority of genetic studies have been conducted on patients with European ancestry, limiting the understanding of the genetic heterogeneity of EOPD across populations. The aim of this study was to screen the PRKN and PINK1 genes in an Ecuadorian EOPD cohort, and improve the understanding of the genetic profile of patients in this population.

Material and methods: Seventy unrelated patients with EOPD and with an average age at onset of 42.6 ± 5.6 years were recruited at the Hospital Eugenio Espejo in Quito, Ecuador, and screened for the presence of PRKN and PINK1 single nucleotide and copy number variations.

Results: Sanger sequencing identified six PRKN variants, and five resulted in nonsynonymous amino acid substitutions. Seven PINK1 variants were identified: four nonsynonymous, and three common (MAF > 1%), among the EOPD cohort. Multiplex ligation-dependent probe amplification (MLPA) identified three carriers with PRKN copy number variants. Overall, across the series, two patients carried pathogenic homozygous deletions of exons 3 and 4.

Discussion: Gaining insights into the genetics of EOPD in Latin America is important. In this study, we have identified two carriers of pathogenic PRKN copy number variants in a relatively large group of Ecuadorian patients with EOPD. Additional, familial, early-onset and sporadic PD studies are warranted to further expand the knowledge base regarding Latin American populations.