Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease

Am J Hum Genet. 2005 Apr;76(4):572-80. doi: 10.1086/429130. Epub 2005 Feb 10.


CREB-binding protein and p300 function as transcriptional coactivators in the regulation of gene expression through various signal-transduction pathways. Both are potent histone acetyl transferases. A certain level of CREB-binding protein is essential for normal development, since inactivation of one allele causes Rubinstein-Taybi syndrome (RSTS). There is a direct link between loss of acetyl transferase activity and RSTS, which indicates that the disorder is caused by aberrant chromatin regulation. We screened the entire CREB-binding protein gene (CBP) for mutations in patients with RSTS by using methods that find point mutations and larger rearrangements. In 92 patients, we were able to identify a total of 36 mutations in CBP. By using multiple ligation-dependent probe amplification, we found not only several deletions but also the first reported intragenic duplication in a patient with RSTS. We extended the search for mutations to the EP300 gene and showed that mutations in EP300 also cause this disorder. These are the first mutations identified in EP300 for a congenital disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Amino Acid Sequence
  • CREB-Binding Protein
  • Female
  • Genetic Heterogeneity
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics*
  • Pedigree
  • Rubinstein-Taybi Syndrome / genetics*
  • Trans-Activators / genetics*


  • Nuclear Proteins
  • Trans-Activators
  • Acetyltransferases
  • CREB-Binding Protein
  • CREBBP protein, human

Associated data

  • RefSeq/NM_004380