Somatic mosaicism in ALS and FTD identifies focal mutations associated with widespread degeneration - PubMed
4 hours ago
- #ALS/FTD genetics
- #neurodegeneration
- #somatic mosaicism
- Somatic mosaicism involves rare, low-frequency somatic mutations in genes linked to neurodegeneration, observed in 2.1% of sporadic ALS and FTD cases without germline variants.
- Mutations typically occur at allele fractions below 2%, are focal, and enriched in disease-affected brain and spinal cord regions.
- Screening identified deleterious somatic variants in DYNC1H1 and LMNA, genes also associated with pediatric motor neuron disorders, and one case of somatic C9orf72 repeat expansions in sporadic FTD.
- Research suggests these focal somatic variants can contribute to sporadic ALS and FTD, potentially driving widespread neurodegeneration despite their localized origin.