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Genetic heterogeneity in Rubinstein-Taybi Syndrome: Delineation of the phenotype of the first patients carrying mutations in EP300
  1. Deborah Bartholdi (bartholdi{at}medgen.unizh.ch)
  1. Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland
    1. Jeroen H Roelfsema
    1. Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands
      1. Francesco Papadia
      1. Department of Metabolic Diseases and Clinical Genetics, Pediatric Hospital Giovanni XXIII, Bari, Italy
        1. Martijn H Breuning
        1. Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands
          1. Dunja Niedrist
          1. Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland
            1. Raoul C Hennekam
            1. Clinical and Molecular Genetics Unit, Institute of Child Health, UCL, London, UK, and Department of
              1. Albert Schinzel
              1. Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland
                1. Dorien J.M. Peters
                1. Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands

                  Abstract

                  Background: Rubinstein-Taybi syndrome (RSTS) is a congenital disorder characterized by growth retardation, facial dysmorphisms, skeletal abnormalities and mental retardation. Broad thumbs and halluces are the hallmarks of the syndrome. RSTS is associated with chromosomal rearrangements and mutations in the CREBBP gene, also termed CBP, encoding the CREB-binding protein. Recently, it was shown that mutations in EP300, coding for the p300 protein, are also causing RSTS. CBP and EP300 are highly homologous genes which play important roles as global transcriptional coactivators. Objective: To report the phenotype of the presently known RSTS patients (n=4) carrying germline mutations of EP300. Results: The EP300 patients displayed the typical facial gestalt and malformation pattern compatible with the diagnosis of RSTS. However, three patients exhibited much milder skeletal findings on the hands and feet than typically observed in RSTS. Conclusions: Part of the clinical variability in RSTS is explained by genetic heterogeneity. The diagnosis of RSTS must be expanded to include patients without broad thumbs or halluces.

                  • CBP
                  • CREBBP
                  • Rubinstein-Taybi syndrome
                  • genotype-phenotype correlation
                  • p300

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