A Genetic Analysis Of A Spanish Population With Early Onset Parkinson'S Disease

Introduction 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 inPARK2,LRRK2,PINK1, orGBA. The gene most frequently mutated wasPARK2, and p.Asn52Metfs*29 was the most common variation in this gene. Pathogenic variants were not observed in genesSNCA,FBXO7,PARK7,HTRA2,DNAJC6,PLA2G6, andUCHL1. Co-occurrence of pathogenic variants involving two genes was observed inATP13A2andPARK2genes, as well asLRRK2andGIGYF2genes. Conclusions Our results contribute to the understanding of the genetic architecture associated with early onset Parkinson's disease, showing bothPARK2andLRRK2play an important role in Spanish Parkinson's disease patients. Rare variants inATP13A2andGIGYF2may 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.