Somatic Mosaicism in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Reveals Widespread Degeneration from Focal Mutations.

ABSTRACT: Although mutations in dozens of genes have been implicated in familial forms of amyotrophic lateral sclerosis (fALS) and frontotemporal degeneration (fFTD), most cases of these conditions are sporadic (sALS and sFTD), with no family history, and their etiology remains obscure. We tested the hypothesis that somatic mosaic mutations, present in some but not all cells, might contribute in these cases, by performing ultra-deep, targeted sequencing of 88 genes associated with neurodegenerative diseases in postmortem brain and spinal cord samples from 404 individuals with sALS or sFTD and 144 controls. Known pathogenic germline mutations were found in 20.6% of ALS, and 26.5% of FTD cases. Predicted pathogenic somatic mutations in ALS/FTD genes were observed in 2.7% of sALS and sFTD cases that di

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC10705414 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature