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

Childhood Overgrowth Collaboration, 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 RankinMiranda Splitt, Volker Strenger, Clare Taylor, Patricia Wheeler, Karen I Temple, Trevor Cole, Jenny Douglas, Nazneen Rahman

Research output: Contribution to journalArticlepeer-review

123 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1127-33
Number of pages7
Issue number12
Publication statusPublished - Dec 2011


  • Abnormalities, Multiple/genetics
  • Amino Acid Sequence
  • Body Height
  • Congenital Hypothyroidism/genetics
  • Craniofacial Abnormalities/genetics
  • DNA-Binding Proteins/genetics
  • Enhancer of Zeste Homolog 2 Protein
  • Facies
  • Female
  • Germ-Line Mutation
  • Growth Disorders/genetics
  • Hand Deformities, Congenital/genetics
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase/genetics
  • Histones/genetics
  • Humans
  • Male
  • Polycomb Repressive Complex 2
  • Sequence Analysis, DNA
  • Transcription Factors/genetics


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