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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.

Burkardt, DD; Zachariou, A; Loveday, C; Allen, CL; Amor, DJ; Ardissone, A; Banka, S; Bourgois, A; Coubes, C; Cytrynbaum, C; et al. Burkardt, DD; Zachariou, A; Loveday, C; Allen, CL; Amor, DJ; Ardissone, A; Banka, S; Bourgois, A; Coubes, C; Cytrynbaum, C; Faivre, L; Marion, G; Horton, R; Kotzot, D; Lay-Son, G; Lees, M; Low, K; Luk, H-M; Mark, P; McConkie-Rosell, A; McDonald, M; Pappas, J; Phillipe, C; Shears, D; Skotko, B; Stewart, F; Stewart, H; Temple, IK; Mau-Them, FT; Verdugo, RA; Weksberg, R; Zarate, YA; Graham, JM; Tatton-Brown, K (2019) 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. Am J Med Genet A, 179 (10). pp. 2049-2055. ISSN 1552-4833 https://doi.org/10.1002/ajmg.a.61321
SGUL Authors: Tatton-Brown, Katrina Louise

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Abstract

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.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Burkardt, DD, Zachariou, A, Loveday, C, et al. 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. Am J Med Genet Part A. 2019; 179A: 2049– 2055, which has been published in final form at https://doi.org/10.1002/ajmg.a.61321. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Keywords: HIST1H1E, Rahman syndrome, epigenetic regulator gene, intellectual disability, Behavior, Facies, Growth and Development, Heterozygote, Histones, Humans, Intellectual Disability, Learning, Mutation, Phenotype, Syndrome, Humans, Syndrome, Facies, Histones, Behavior, Learning, Growth and Development, Heterozygote, Phenotype, Mutation, Intellectual Disability, epigenetic regulator gene, intellectual disability, Rahman syndrome, HIST1H1E, Rahman syndrome, epigenetic regulator gene, intellectual disability, 1103 Clinical Sciences, 0604 Genetics
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Journal or Publication Title: Am J Med Genet A
ISSN: 1552-4833
Language: eng
Dates:
DateEvent
10 September 2019Published
9 August 2019Published Online
27 July 2019Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
GR01/13Child Growth FoundationUNSPECIFIED
100210/Z/12/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
HICF-1009-003Health Innovation Challenge FundUNSPECIFIED
UNSPECIFIEDBiomedical Research CentreUNSPECIFIED
PubMed ID: 31400068
Web of Science ID: WOS:000480993600001
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112717
Publisher's version: https://doi.org/10.1002/ajmg.a.61321

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