Open AccessA genetic analysis of a Spanish population with early onset Parkinson’s disease
Author(s) -
Cristina TejeraParrado,
M. R. de Pablo,
Periñán María Teresa,
Lydia Vela-Desojo,
Irene Abreu-Rodríguez,
Araceli AlonsoCánovas,
Inmaculada BernalBernal,
Marta BonillaToribio,
Dolores BuizaRueda,
Catalán-Alonso María José,
R. García-Ramos,
García-Ruiz Pedro José,
Ismael HuertasFernández,
Silvia Jesús,
Miguel A. Espinosa Labrador,
Lydia López-Manzanares,
Martínez-Castrillo Juan Carlos,
Ignacio J. Posada,
Ana Rojo-Sebastián,
Cristina RodríguezPadilla,
Del Val Javier,
Pilar GómezGarre
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0238098
Subject(s) - lrrk2 , disease , parkinson's disease , genetics , pink1 , age of onset , biology , medicine , parkin , population , genetic testing , pathology , environmental health
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. Methods/patients 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. Results 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. Conclusions 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.