De novo missense variant identified in HIST1H4J. a Pedigree and photographs of the proband. The tilted square refers to unspecified sex. b Location of the de novo missense variant at gene and protein level and alignment of H4 residues demonstrating that K91 as well as surrounding residues are highly conserved across species. At the genomic level, this A > G substitution is located at chr6:27792176 (hg19). See main text for more information on the nomenclature

The K91E substitution on HIST1H4J induces early severe developmental defects in zebrafish embryos. a Phenotypes observed in zebrafish embryos at 28 h post fertilization. Wildtype HIST1H4J (WT) and K91E mRNA was microinjected at the 1-cell stage. Class 1 embryos display normal development, class 2 embryos display mild shortening of the body axis and delayed head development. Class 3 embryos have severely defective head development and a shortened AP body axis, with abnormal posterior development. In Class 4 embryos head structures and somites are largely absent. b Histogram presenting the percentage of observed embryos in each class for each category. no inj non-injected control. The data presented were collected over three independent biological and technical experimental replicates