Journal Article

A genetic analysis of a Spanish population with early onset Parkinson’s disease

Inmaculada, Bernal-Bernal, Cristina, Tejera-Parrado, José, Catalán-Alonso María, Silvia, Jesús, Ana, Rojo-Sebastián, José, García-Ruiz Pedro, Rocío, García-Ramos, Ismael, Huertas-Fernández, Lydia, López-Manzanares, Labrador, Miguel A-Espinosa, Gómez-Garre, Pilar, Dolores, Buiza-Rueda, Lydia, Vela-Desojo, Araceli, Alonso-Cánovas, Javier, Del Val, Pablo, Mir, Marta, Bonilla-Toribio, Carlos, Martínez-Castrillo Juan, Irene, Abreu-Rodríguez, Posada, Ignacio J., Cristina, Ruiz-Huete, Teresa, Periñán María

2020

Overview

Both recessive and dominant genetic forms of Parkinson's disease have been described. The aim of this study was to assess the contribution of several genes to the pathophysiology of early onset Parkinson's disease in a cohort from central Spain. We analyzed a cohort of 117 unrelated patients with early onset Parkinson's disease using a pipeline, based on a combination of a next-generation sequencing panel of 17 genes previously related with Parkinson's disease and other Parkinsonisms and CNV screening. Twenty-six patients (22.22%) carried likely pathogenic variants in PARK2, LRRK2, PINK1, or GBA. The gene most frequently mutated was PARK2, and p.Asn52Metfs*29 was the most common variation in this gene. Pathogenic variants were not observed in genes SNCA, FBXO7, PARK7, HTRA2, DNAJC6, PLA2G6, and UCHL1. Co-occurrence of pathogenic variants involving two genes was observed in ATP13A2 and PARK2 genes, as well as LRRK2 and GIGYF2 genes. Our results contribute to the understanding of the genetic architecture associated with early onset Parkinson's disease, showing both PARK2 and LRRK2 play an important role in Spanish Parkinson's disease patients. Rare variants in ATP13A2 and GIGYF2 may contribute to PD risk. However, a large proportion of genetic components remains unknown. This study might contribute to genetic diagnosis and counseling for families with early onset Parkinson's disease.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Age of Onset / Analysis / Biology and Life Sciences / Cohort Studies / Deoxyribonucleic acid / Development and progression / DNA / Female / Genes / Genetic analysis / Genetic aspects / Genetic screening / Genetic Testing / Genetic Variation / Genomes / Health risks / High-Throughput Nucleotide Sequencing / Humans / LRRK2 protein / Male / Medicine and Health Sciences / Middle Aged / Movement disorders / Mutation / Neurodegenerative diseases / Next-generation sequencing / PARK7 protein / Parkinson disease / Parkinson Disease - epidemiology / Parkinson Disease - genetics / Parkinson's disease / People and places / Proteins / PTEN-induced putative kinase / Research and analysis methods / Spain - epidemiology