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 individuals.
HIST1H1E
Rahman syndrome
epigenetic regulator gene
intellectual disability
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
19
07
2019
revised:
25
07
2019
accepted:
27
07
2019
pubmed:
11
8
2019
medline:
4
8
2020
entrez:
11
8
2019
Statut:
ppublish
Résumé
Histone Gene Cluster 1 Member E, HIST1H1E, encodes Histone H1.4, is one of a family of epigenetic regulator genes, acts as a linker histone protein, and is responsible for higher order chromatin structure. HIST1H1E syndrome (also known as Rahman syndrome, OMIM #617537) is a recently described intellectual disability (ID) syndrome. Since the initial description of five unrelated individuals with three different heterozygous protein-truncating variants (PTVs) in the HIST1H1E gene in 2017, we have recruited 30 patients, all with HIST1H1E PTVs that result in the same shift in frame and that cluster to a 94-base pair region in the HIST1H1E carboxy terminal domain. The identification of 30 patients with HIST1H1E variants has allowed the clarification of the HIST1H1E syndrome phenotype. Major findings include an ID and a recognizable facial appearance. ID was reported in all patients and is most frequently of moderate severity. The facial gestalt consists of a high frontal hairline and full lower cheeks in early childhood and, in later childhood and adulthood, affected individuals have a strikingly high frontal hairline, frontal bossing, and deep-set eyes. Other associated clinical features include hypothyroidism, abnormal dentition, behavioral issues, cryptorchidism, skeletal anomalies, and cardiac anomalies. Brain magnetic resonance imaging (MRI) is frequently abnormal with a slender corpus callosum a frequent finding.
Identifiants
pubmed: 31400068
doi: 10.1002/ajmg.a.61321
doi:
Substances chimiques
H1-4 protein, human
0
Histones
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2049-2055Subventions
Organisme : Child Growth Foundation
ID : GR01/13
Pays : International
Organisme : Wellcome Trust
ID : 100210/Z/12/Z
Pays : United Kingdom
Organisme : Health Innovation Challenge Fund
ID : HICF-1009-003
Pays : International
Organisme : Biomedical Research Centre
Pays : International
Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
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