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Rubinstein–Taybi syndrome: clinical and molecular overview

Published online by Cambridge University Press:  20 August 2007

Jeroen H. Roelfsema  and
Dorien J.M. Peters
Jeroen H. Roelfsema
Affiliation:
Dept of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Dorien J.M. Peters*
Affiliation:
Dept of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
*
*Corresponding author: Dorien Peters, Dept of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Postzone S-04-P, PO Box 9600, 2300 RC Leiden, The Netherlands. Tel: 31 71 5269490; Fax: 31 71 5268285; E-mail: d.j.m.peters@lumc.nl
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Abstract

Rubinstein–Taybi syndrome is characterised by mental retardation, growth retardation and a particular dysmorphology. The syndrome is rare, with a frequency of approximately one affected individual in 100 000 newborns. Mutations in two genes – CREBBP and EP300 – have been identified to cause the syndrome. These two genes show strong homology and encode histone acetyltransferases (HATs), which are transcriptional co-activators involved in many signalling pathways. Loss of HAT activity is sufficient to account for the phenomena seen in Rubinstein–Taybi patients. Although some mutations found in CREBBP are translocations, inversions and large deletions, most are point mutations or small deletions and insertions. Mutations in EP300 are comparatively rare. Extensive screening of patients has revealed mutations in CREBBP and EP300 in around 50% of cases. The cause of the syndrome in the remaining patients remains to be identified, but other genes could also be involved. Here, we describe the clinical presentation of Rubinstein–Taybi syndrome, review the mutation spectrum and discuss the current understanding of causative molecular mechanisms.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 9 , Issue 23 , August 2007 , pp. 1 - 16
Copyright
Copyright © Cambridge University Press 2007

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References

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Further reading, resources and contacts

The Online Mendelian Inheritance in Man (OMIM) website provides a description of Rubinstein–Taybi syndrome (Rubinstein–Taybi syndrome, OMIM 180849; CREBBP or CBP, OMIM 600140; EP300 or p300, OMIM 602700):

Gorlin, R.J., Cohen, M.M. and Hennekam, R.C.M. (2001). Syndromes of the Head and Neck. [Oxford Monographs on Medical Genetics (No. 42)], Oxford University Press, New YorkCrossRefGoogle Scholar
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Hallam, T.M. and Bourtchouladze, R. (2006) Rubinstein-Taybi syndrome: molecular findings and therapeutic approaches to improve cognitive dysfunction. Cell Mol Life Sci 63, 1725–1735.Google Scholar
http://ww.ncbi.nlm.gov/OmimGoogle Scholar
http://www.LOVD.nl/CREBBP and http://www.LOVD.nl/EP300Google Scholar
www.GeneTests.orgGoogle Scholar
http://www.stjude.org/brindleGoogle Scholar
http://ww.ncbi.nlm.gov/OmimGoogle Scholar
http://www.LOVD.nl/CREBBP and http://www.LOVD.nl/EP300Google Scholar
www.GeneTests.orgGoogle Scholar
http://www.stjude.org/brindleGoogle Scholar