Sleep disturbances associated with DEAF1 pathogenic variants

Neurodevelopmental disorders and sleep disturbances share genetic risk factors. DEAF1 genetic variants are associated with rare syndromes in which sleep disturbances are commonly reported, yet the specific sleep disorders in these patients, and the molecular mechanisms underlying this association, are unknown. We aimed to pinpoint specific biological processes that may be disrupted by pathogenic variants in this gene, comparing a list of DEAF1 regulatory target genes with a list of insomnia-associated genes, and using the intersect gene list as the input for pathway enrichment analysis. Thirty-nine DEAF1 regulatory targets were also identified as insomnia-associated genes, and the intersecting gene list was found to be strongly associated with immune processes, ubiquitin-mediated proteolysis pathways, and regulation of the cell cycle. This preliminary study highlights pathways that may be disrupted by DEAF1 pathogenic mutations and might be putative factors underlying the manifestation of insomnia in patients harboring such variants.

Guerreiro P, Moysés-Oliveira M, Paschalidis M, et al. Sleep disturbances associated with DEAF1 pathogenic variants. J Clin Sleep Med. 2025;21(1):207-210.