AUTHOR=Lobon Irene , Solís-Moruno Manuel , Juan David , Muhaisen Ashraf , Abascal Federico , Esteller-Cucala Paula , García-Pérez Raquel , Martí Maria Josep , Tolosa Eduardo , Ávila Jesús , Rahbari Raheleh , Marques-Bonet Tomas , Casals Ferran , Soriano Eduardo TITLE=Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes JOURNAL=Frontiers in Aging VOLUME=3 YEAR=2022 URL=https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2022.851039 DOI=10.3389/fragi.2022.851039 ISSN=2673-6217 ABSTRACT=

The role of somatic mutations in complex diseases, including neurodevelopmental and neurodegenerative disorders, is becoming increasingly clear. However, to date, no study has shown their relation to Parkinson disease’s phenotype. To explore the relevance of embryonic somatic mutations in sporadic Parkinson disease, we performed whole-exome sequencing in blood and four brain regions of ten patients. We identified 59 candidate somatic single nucleotide variants (sSNVs) through sensitive calling and a careful filtering strategy (COSMOS). We validated 27 of them with amplicon-based ultra-deep sequencing, with a 70% validation rate for the highest-confidence variants. The identified sSNVs are in genes with synaptic functions that are co-expressed with genes previously associated with Parkinson disease. Most of the sSNVs were only called in blood but were also found in the brain tissues with ultra-deep amplicon sequencing, demonstrating the strength of multi-tissue sampling designs.