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Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.

Tatton-Brown, K; Hanks, S; Ruark, E; Zachariou, A; Duarte, SDELV; Ramsay, E; Snape, K; Murray, A; Perdeaux, ER; Seal, S; et al. Tatton-Brown, K; Hanks, S; Ruark, E; Zachariou, A; Duarte, SDELV; Ramsay, E; Snape, K; Murray, A; Perdeaux, ER; Seal, S; Loveday, C; Banka, S; Clericuzio, C; Flinter, F; Magee, A; McConnell, V; Patton, M; Raith, W; Rankin, J; Splitt, M; Strenger, V; Taylor, C; Wheeler, P; Temple, KI; Cole, T; Childhood Overgrowth Collaboration; Douglas, J; Rahman, N (2011) Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height. Oncotarget, 2 (12). pp. 1127-1133. ISSN 1949-2553 https://doi.org/10.18632/oncotarget.385
SGUL Authors: Patton, Michael Alexander Snape, Katie Mairwen Greenwood Tatton-Brown, Katrina Louise

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Abstract

The biological processes controlling human growth are diverse, complex and poorly understood. Genetic factors are important and human height has been shown to be a highly polygenic trait to which common and rare genetic variation contributes. Weaver syndrome is a human overgrowth condition characterised by tall stature, dysmorphic facial features, learning disability and variable additional features. We performed exome sequencing in four individuals with Weaver syndrome, identifying a mutation in the histone methyltransferase, EZH2, in each case. Sequencing of EZH2 in additional individuals with overgrowth identified a further 15 mutations. The EZH2 mutation spectrum in Weaver syndrome shows considerable overlap with the inactivating somatic EZH2 mutations recently reported in myeloid malignancies. Our data establish EZH2 mutations as the cause of Weaver syndrome and provide further links between histone modifications and regulation of human growth.

Item Type: Article
Additional Information: © Tatton-Brown et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Correction available at: http://doi.org/10.18632/oncotarget.26429 | http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=26429
Keywords: Abnormalities, Multiple, Amino Acid Sequence, Body Height, Congenital Hypothyroidism, Craniofacial Abnormalities, DNA-Binding Proteins, Facies, Female, Germ-Line Mutation, Growth Disorders, Hand Deformities, Congenital, Histone-Lysine N-Methyltransferase, Histones, Humans, Male, Polycomb Repressive Complex 2, Sequence Analysis, DNA, Transcription Factors, EZH2, Weaver syndrome, height, myeloid malignancies, histone methyltransferase, Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, AUTOSOMAL-DOMINANT INHERITANCE, METHYLTRANSFERASE GENE EZH2, B-CELL LYMPHOMAS, SOMATIC MUTATIONS, SPLICING SIGNALS, HISTONE H3, METHYLATION, DNA, PREDICTION, PHENOTYPE
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Clinical Education (INMECE )
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: Oncotarget
ISSN: 1949-2553
Language: eng
Dates:
DateEvent
21 December 2011Published
PubMed ID: 22190405
Web of Science ID: WOS:000299424200021
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/107294
Publisher's version: https://doi.org/10.18632/oncotarget.385

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