Research Papers:

This article has been corrected. Correction in: Oncotarget. 2018; 9:36719.

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

Katrina Tatton-Brown, Sandra Hanks, Elise Ruark, Anna Zachariou, Silvana Del Vecchio Duarte, Emma Ramsay, Katie Snape, Anne Murray, Elizabeth R. Perdeaux, Sheila Seal, Chey Loveday, Siddharth Banka, Carol Clericuzio, Frances Flinter, Alex Magee, Vivienne McConnell, Michael Patton, Wolfgang Raith, Julia Rankin, Miranda Splitt, Volker Strenger, Clare Taylor, Patricia Wheeler, I. Karen Temple, Trevor Cole, Jenny Douglas and Nazneen Rahman _

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Oncotarget. 2011; 2:1127-1133. https://doi.org/10.18632/oncotarget.385

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Katrina Tatton-Brown1,2, Sandra Hanks1, Elise Ruark1, Anna Zachariou1, Silvana Del Vecchio Duarte1, Emma Ramsay1, Katie Snape1, Anne Murray1, Elizabeth R Perdeaux1, Sheila Seal1, Chey Loveday1, Siddharth Banka3, Carol Clericuzio4, Frances Flinter5, Alex Magee6, Vivienne McConnell6, Michael Patton2, Wolfgang Raith7, Julia Rankin8, Miranda Splitt9, Volker Strenger10, Clare Taylor11, Patricia Wheeler12, I Karen Temple13, Trevor Cole14, The Childhood Overgrowth Collaboration15, Jenny Douglas1 and Nazneen Rahman1

1Division of Genetics & Epidemiology, Institute of Cancer Research, Sutton, UK

2Medical Genetics, St George’s University of London, London, UK

3Genetic Medicine, University of Manchester, Manchester, UK

4Pediatric Genetics, University of New Mexico, Albuquerque, USA

5Clinical Genetics, Guy’s and St Thomas’ Foundation Trust, London, UK

6Northern Ireland Regional Genetics Service, Belfast City Hospital, Belfast, Northern Ireland, UK

7Division of Neonatology, Department of Paediatrics, Medical University, Graz, Austria

8Peninsula Clinical Genetics Service, Royal Devon and Exeter Foundation NHS Trust, Exeter, UK

9Institute of Human Genetics, International Centre for Life, Newcastle upon Tyne, UK

10Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria

11Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK

12Division of Genetics, Nemours Children's Clinic, Orlando, USA

13Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, UK

14West Midlands Regional Genetics Service, Birmingham Women’s Hospital, Birmingham, UK

15A full list of members appears in the Supplementary Appendix

Received: December 17, 2011; Accepted: December 20, 2011; Published: December 21, 2011;

Keywords: EZH2, Weaver syndrome, height, myeloid malignancies, histone methyltransferase


Professor Nazneen Rahman, email:


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.

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