Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene

Clin Genet. 2015 Feb;87(2):148-54. doi: 10.1111/cge.12348. Epub 2014 Feb 17.


Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder characterized by postnatal growth deficiency, skeletal abnormalities, dysmorphic features and cognitive deficit. Mutations in two genes, CREBBP and EP300, encoding two homologous transcriptional co-activators, have been identified in ˜55% and ˜3-5% of affected individuals, respectively. To date, only eight EP300-mutated RSTS patients have been described and 12 additional mutations are reported in the database LOVD. In this study, EP300 analysis was performed on 33 CREBBP-negative RSTS patients leading to the identification of six unreported germline EP300 alterations comprising one deletion and five point mutations. All six patients showed a convincing, albeit mild, RSTS phenotype with minor skeletal anomalies, slight cognitive impairment and few major malformations. Beyond the expansion of the RSTS-EP300-mutated cohort, this study indicates that EP300-related RSTS cases occur more frequently than previously thought (˜8% vs 3-5%); furthermore, the characterization of novel EP300 mutations in RSTS patients will enhance the clinical practice and genotype-phenotype correlations.

Keywords: EP300; Rubinstein-Taybi syndrome; exonic deletions; genotype-phenotype correlations; point mutations.

MeSH terms

  • Adolescent
  • Adult
  • CREB-Binding Protein / genetics*
  • Child
  • Child, Preschool
  • E1A-Associated p300 Protein / genetics*
  • Female
  • Genetic Association Studies
  • Humans
  • Infant
  • Male
  • Mutation
  • Rubinstein-Taybi Syndrome / genetics*
  • Rubinstein-Taybi Syndrome / physiopathology
  • Sequence Deletion


  • CREB-Binding Protein
  • CREBBP protein, human
  • E1A-Associated p300 Protein
  • EP300 protein, human