Lobon Garcia, IreneSolís Moruno, Manuel, 1993-Juan, DavidMuhaisen, AshrafAbascal, FedericoEsteller Cucala, PaulaGarcía Pérez, Raquel, 1989-Martí, Maria JoséTolosa, EduardÁvila, JesúsRahbari, RahelehMarquès i Bonet, Tomàs, 1975-Casals López, FerranSoriano, Eduardo2023-07-072023-07-072022Lobon I, Solís-Moruno M, Juan D, Muhaisen A, Abascal F, Esteller-Cucala P, García-Pérez R, Martí MJ, Tolosa E, Ávila J, Rahbari R, Marques-Bonet T, Casals F, Soriano E. Somatic mutations detected in Parkinson disease could affect genes with a role in synaptic and neuronal processes. Front Aging. 2022 Apr 28;3:851039. DOI: 10.3389/fragi.2022.8510392673-6217http://hdl.handle.net/10230/57494The 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.application/pdfeng© 2022 Lobon, Solís-Moruno, Juan, Muhaisen, Abascal, Esteller-Cucala, García-Pérez, Martí, Tolosa, Ávila, Rahbari, Marques-Bonet, Casals and Soriano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.info:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fragi.2022.851039Parkinson diseaseBrain mosaicismNeurodegenarationSomatic genome alterationSomatic mutationsinfo:eu-repo/semantics/openAccess