Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability
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 produ ct 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.
Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Katrina Tatton-Brown, Chey Loveday, Shawn Yost, Matthew Clarke, Emma Ramsay, Anna Zachariou, Anna Elliott, Harriet Wylie, Anna Ardissone, Olaf Rittinger, Fiona Stewart, I. Karen Temple, Trevor Cole, Childhood Overgrowth Collaboration, Shazia Mahamdallie, Tags: Article Source Type: research