LEO1 haploinsufficiency is associated with developmental delays and autism spectrum disorder.

ABSTRACT: LEO1 encodes a core subunit of the evolutionarily conserved RNA polymerase associated factor 1 complex (PAF1C), a key regulator of eukaryotic gene expression. While burden analyses suggest an association between rare LEO1 variants and an increased risk for neurodevelopmental disorder, the paucity of reported cases has prevented a definitive characterization of the resulting phenotype. We describe a male child with a novel de novo frameshift variant in LEO1 c.446dup (p.Asp149Gluf s*2) and undertake a comprehensive phenotype delineation of all previously reported patients. Developmental delay and autism spectrum disorder were core features common across patients with truncating variants, though rarer manifestations were also observed. This analysis supports LEO1 haploinsufficiency as a mecha

SUBMITTER: Ung EC 

PROVIDER: S-EPMC12765696 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature