ClinVar

In 7 unrelated patients (P16-P22) with Tessadori-Bicknell-van Haaften neurodevelopmental syndrome-3 (TEBIVANED3; 619950), Tessadori et al. (2022) identified a de novo heterozygous c.136C-T transition (c.136C-T, NM_003545.3) in the H4C5 gene, resulting in an arg46-to-cys (R46C) substitution at a conserved residue in the core globular domain. The mutation, which was found by exome sequencing, was not present in the gnomAD database. Expression of the mutation in zebrafish embryos induced mild developmental defects that just reached significance (p less that 0.05), suggesting that it may be pathogenic. The authors postulated a dominant effect. The patients had poor overall growth and global developmental delay, but there was phenotypic heterogeneity. The authors also referred to this mutation as ARG45CYS (R45C), reflecting the practice of dropping the numbering of the first posttranslationally removed methionine.