Heterozygous mutations in the H1-4 gene are responsible for Rahman syndrome (OMIM 617537), a disorder characterized by mild to severe intellectual disability associated with variable somatic overgrowth manifest as increased birth length, height, weight, and/or head circumference (Tatton-Brown et al., 2017). Autism spectrum disorder has been observed in a subset of individuals with H1-4 variants (Duffney et al., 2018; Burkardt et al., 2019; Tremblay et al., 2021).
Molecular Function
Histones are basic nuclear proteins responsible for nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H1 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Epigenetics and autism spectrum disorder: A report of an autism case with mutation in H1 linker histone HIST1H1E and literature review
Expanding the mutational spectrum of Rahman syndrome: A rare disorder with severe intellectual disability and particular facial features in two Chinese patients
HIST1H1E heterozygous protein-truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 in
ID
ASD or autistic features, stereotypy, epilepsy/sei
Mutations of the histone linker H1-4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4
