Journal article

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 Show all



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..

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Awarded by Medical Research Council

Funding Acknowledgements

We thank the families and the physicians and nurses that recruited them, for their participation in this study which was funded by the Institute of Cancer Research. We thank Deborah Hughes and Bernadette Ebbs for assistance in DNA extraction and running the ABI sequencers. We thank Ann Strydom for assistance with the manuscript. The case samples were collected through the Childhood Overgrowth Collaboration, the full list of contributors is given in the Supplementary Appendix. We acknowledge NHS funding to the ICR/RMH NIHR Specialist Biomedical Cancer Research Centre.