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 - Université de Bourgogne Accéder directement au contenu
Article Dans Une Revue American Journal of Medical Genetics Part A Année : 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

1 Case Western Reserve University [Cleveland]
2 The institute of cancer research [London]
3 UCLH - University College London Hospitals
4 MCRI - Murdoch Children's Research Institute
5 University of Melbourne
6 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
7 University of Manchester [Manchester]
8 MFT - Manchester University NHS Foundation Trust
9 Service de Génétique [CHU Caen]
10 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
11 SickKids - The Hospital for sick children [Toronto]
12 Hôpital d'Enfants [CHU Dijon]
13 BIOTARGEN - Biologie, génétique et thérapies ostéoarticulaires et respiratoires
14 University Hospital Southampton NHS Foundation Trust
15 PMU - Paracelsus Medizinische Privatuniversität = Paracelsus Medical University
16 UC - Pontificia Universidad Católica de Chile
17 GOSH - Great Ormond Street Hospital for Children [London]
18 University Hospitals Bristol
19 Department of Health Clinical Genetic Service Centre
20 Spectrum Health [Grand Rapids]
21 MGM - Department of Molecular Genetics and Microbiology [Durham]
22 NYU - New York University School of Medicine
23 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
24 Department of Clinical Genetics [Churchill Hospital]
25 HMS - Harvard Medical School [Boston]
26 Belfast City Hospital
27 Oxford University Hospitals NHS Trust
28 University of Southampton
29 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
30 UCHILE - Universidad de Chile = University of Chile [Santiago]
31 Arkansas Children's Hospital
32 Cedars-Sinai Medical Center
33 St George’s University Hospitals
Laurence Faivre

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.

Dates et versions

hal-02393762 , version 1 (04-12-2019)

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Citer

Deepika d'Cunha Burkardt, Anna Zachariou, Chey Loveday, Clare Allen, David Amor, 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. American Journal of Medical Genetics Part A, 2019, 179 (10), pp.2049-2055. ⟨10.1002/ajmg.a.61321⟩. ⟨hal-02393762⟩
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