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Intellectual disability

Gene: HIST1H4C

Amber List (moderate evidence)

HIST1H4C (histone cluster 1 H4 family member c)
EnsemblGeneIds (GRCh38): ENSG00000197061
EnsemblGeneIds (GRCh37): ENSG00000197061
OMIM: 602827, Gene2Phenotype
HIST1H4C is in 3 panels

2 reviews

Helen Brittain (Genomics England Curator)

Comment when marking as ready: Only two families to date, considered appropriate for amber and watchlist.
Created: 5 Mar 2018, 12:38 p.m.

Louise Daugherty (Genomics England Curator)

Added new-gene-name tag, new approved HGNC gene symbol for HIST1H4C is H4C3
Created: 6 Sep 2019, 3:29 p.m. | Last Modified: 6 Sep 2019, 3:29 p.m.
Panel Version: 2.1022
This is a probable DD gene in Gene2Phenotype for a HIST1H4C Disease, all missense/in frame variants.
Created: 20 Feb 2018, 3:36 p.m.
Comment on list classification: Currently only two unrelated cases to support HIST1H4C variants causing an observed ID phenotype. There is also animal model in zebrafish that supports the observed phenotype in the patients.
Created: 20 Feb 2018, 3:23 p.m.
added watchlist tag
Created: 20 Feb 2018, 3:12 p.m.
Comment on phenotypes: added phenotypes as listed in PMID:28920961
Created: 20 Feb 2018, 3:12 p.m.
Comment on publications: added publication to support possible association to ID. Tessadori F, et al., 2017 (PMID: 28920961) reported monoallelic missense mutations affecting lysine 91 in the histone H4 core (H4K91) in 2 individuals (3 affecteds) with a syndrome of growth delay, microcephaly and intellectual disability.
The results highlight the alteration of K91 on histone H4 acts in a genetically dominant manner the results suggest a mechanism involving inherent DNA damage accumulation and early perturbation of the cell cycle, through which missense mutations in HIST1H4C affecting K91 of histone H4 are causative for an identifiable syndrome consisting of dysmorphic features and intellectual disability.
They concluded that the presence of two siblings (patients 2 and 3) from unrelated Dutch parents and another independent patient (patient 1) displaying similar clinical phenotypes, in combination with in vivo modeling evidence in zebrafish embryos, indicates that the substitutions affecting the gene HIST1H4C cause the abnormal phenotypes in patients.

Created: 20 Feb 2018, 2:52 p.m.

Details

Sources
  • Victorian Clinical Genetics Services
  • Gene2Phenotype
  • Expert Review Amber
Phenotypes
  • Growth delay, microcephaly and intellectual disability
Tags
watchlist new-gene-name
OMIM
602827
Clinvar variants
Variants in HIST1H4C
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Sep 2019, Gel status: 2

Added Tag

Louise Daugherty (Genomics England Curator)

Tag new-gene-name tag was added to gene: HIST1H4C.

28 Sep 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to HIST1H4C.

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

12 Mar 2018, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

HIST1H4C was added to Intellectual disability panel. Sources: Expert Review Amber,Gene2Phenotype

12 Mar 2018, Gel status: 2

Created

Ellen McDonagh (Genomics England Curator)

HIST1H4C was created by Ellen McDonagh