Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP
Abstract
The Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome with facial abnormalities, broad thumbs, broad big toes and mental retardation as the main clinical features. Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16p13.3 (refs 4-8). Here we report that all these breakpoints are restricted to a region that contains the gene for the human CREB binding protein (CBP), a nuclear protein participating as a co-activator in cyclic-AMP-regulated gene expression. We show that RTS results not only from gross chromosomal rearrangements of chromosome 16p, but also from point mutations in the CBP gene itself. Because the patients are heterozygous for the mutations, we propose that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.
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Mutations in CREBBP cause Rubenstein-Taybi syndrome, a disorder with prominent autistic features.
“Mutations in CREBBP give rise to Rubenstein-Taybi syndrome, a disorder with prominent autistic features (Petrij et al., 1995).”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Petrij et al., 1995
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- Authors
- Petrif, F., Giles, R. H., Dauwerse, H. G., Saris, J. J., Hennekam, R. C. M., Masuno, M., Tommerup, N., van Ommen, G.-J. B., Goodman, R. H., Peters, D. J. M., & Breuning, M. H.
- Affiliations
- Leiden University (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- Kanagawa Children's Medical Center (JP)
- Oslo University Hospital (NO)
- Oregon Health & Science University (US)
- ORCID
- Venue
- Nature
- Published
- 1995-07
- Volume
- 376
- Issue
- 6538
- Pages
- 348-351
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2072924157
- Cited by
- 1,217
- References
- 27
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 28 · 2023: 25 · 2022: 13 · 2021: 27 · 2020: 32 · 2019: 25 · 2018: 19 · 2017: 30 · 2016: 42 · 2015: 38 · 2014: 55 · 2013: 61 · 2012: 50
- FWCI
- 46.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- Rubinstein-Taybi syndrome, CREB-binding protein, chromosome 16p13.3, microdeletion, chromosomal breakpoints, transcriptional coactivator, intellectual disability, heterozygous mutation, developmental abnormalities, malignancy predisposition
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cell Line, Transformed, Chromosomes, Human, Pair 16, Cosmids, DNA, Female, Heterozygote, Humans, Male, Molecular Sequence Data, Nuclear Proteins, Pedigree, Rubinstein-Taybi Syndrome, Transcription Factors, Translocation, Genetic, Trans-Activators, Chromosome Walking, Point Mutation, Sequence Deletion, CREB-Binding Protein
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