Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes

Overview

Journal Front Aging

Specialty Geriatrics

Date 2022 Jul 13

PMID 35821807

Authors

Irene Lobon

Manuel Solis-Moruno

David Juan

Ashraf Muhaisen

Federico Abascal

Paula Esteller-Cucala

Raquel Garcia-Perez

Maria Josep Marti

Eduardo Tolosa

Jesus Avila

Raheleh Rahbari

Tomas Marques-Bonet

Ferran Casals

Eduardo Soriano

Affiliations

Soon will be listed here.

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.

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