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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 publication




Journal article



Publication Date





1127 - 1133


Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.


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