Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability.

ABSTRACT: To explore the genetic architecture of human overgrowth syndromes and human growth control, we performed experimental and bioinformatic analyses of 710 individuals with overgrowth (height and/or head circumference ≥+2 SD) and intellectual disability (OGID). We identified a causal mutation in 1 of 14 genes in 50% (353/710). This includes HIST1H1E, encoding histone H1.4, which has not been associated with a developmental disorder previously. The pathogenic HIST1H1E mutations are predicted to result in a product that is less effective in neutralizing negatively charged linker DNA because it has a reduced net charge, and in DNA binding and protein-protein interactions because key residues are truncated. Functional network analyses demonstrated that epigenetic regulation is a prominent biologic

SUBMITTER: Tatton-Brown K 

PROVIDER: S-EPMC5420355 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature