Journal article

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

Deepika D'Cunha Burkardt, Anna Zachariou, Chey Loveday, Clare L Allen, David J Amor, Anna Ardissone, Siddharth Banka, Alexia Bourgois, Christine Coubes, Cheryl Cytrynbaum, Laurence Faivre, Gerard Marion, Rachel Horton, Dieter Kotzot, Guillermo Lay-Son, Melissa Lees, Karen Low, Ho-Ming Luk, Paul Mark, Allyn McConkie-Rosell Show all



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 patient..

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Awarded by Child Growth Foundation

Awarded by Wellcome Trust

Awarded by Health Innovation Challenge Fund

Funding Acknowledgements

We thank the patients and families for their active participation in this study and the clinicians that recruited them. We acknowledge support from the NIHR RM/ICR Biomedical Research Centre. K.T.-B. is supported by funding from the Child Growth Foundation (GR01/13) and the work was, in part, supported by a Wellcome Trust Award (100210/Z/12/Z). This study makes use of DECIPHER (, which is funded by Wellcome. The Deciphering Developmental Disorders (DDD) study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003). See Nature PMID:25533962 or for full acknowledgements.