Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP

Fred Petrif, Rachel H. Giles, Hans G. Dauwerse, Jasper J. Saris, Raoul C M Hennekam, Mitsuo Masuno, Niels Tommerup, Gert Jan B Van Ommen, Richard Goodman, Dorien J M Peters, Martijn H. Breuning

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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 features1-3. Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16pl3.3 (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-A IMP-regulated gene expression9-12. 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.

Original languageEnglish (US)
Pages (from-to)348-351
Number of pages4
JournalNature
Volume376
Issue number6538
StatePublished - 1995

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Rubinstein-Taybi Syndrome
CREB-Binding Protein
Mutation
Cyclic IMP
Chromosomes
Hallux
Genes
Developmental Genes
Thumb
Nuclear Proteins
Point Mutation
Intellectual Disability
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Petrif, F., Giles, R. H., Dauwerse, H. G., Saris, J. J., Hennekam, R. C. M., Masuno, M., ... Breuning, M. H. (1995). Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature, 376(6538), 348-351.

Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. / Petrif, Fred; Giles, Rachel H.; Dauwerse, Hans G.; Saris, Jasper J.; Hennekam, Raoul C M; Masuno, Mitsuo; Tommerup, Niels; Van Ommen, Gert Jan B; Goodman, Richard; Peters, Dorien J M; Breuning, Martijn H.

In: Nature, Vol. 376, No. 6538, 1995, p. 348-351.

Research output: Contribution to journalArticle

Petrif, F, Giles, RH, Dauwerse, HG, Saris, JJ, Hennekam, RCM, Masuno, M, Tommerup, N, Van Ommen, GJB, Goodman, R, Peters, DJM & Breuning, MH 1995, 'Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP', Nature, vol. 376, no. 6538, pp. 348-351.
Petrif F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RCM, Masuno M et al. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature. 1995;376(6538):348-351.
Petrif, Fred ; Giles, Rachel H. ; Dauwerse, Hans G. ; Saris, Jasper J. ; Hennekam, Raoul C M ; Masuno, Mitsuo ; Tommerup, Niels ; Van Ommen, Gert Jan B ; Goodman, Richard ; Peters, Dorien J M ; Breuning, Martijn H. / Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. In: Nature. 1995 ; Vol. 376, No. 6538. pp. 348-351.
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AU - Dauwerse, Hans G.

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AU - Masuno, Mitsuo

AU - Tommerup, Niels

AU - Van Ommen, Gert Jan B

AU - Goodman, Richard

AU - Peters, Dorien J M

AU - Breuning, Martijn H.

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AB - 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 features1-3. Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16pl3.3 (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-A IMP-regulated gene expression9-12. 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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