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

Nature volume 376, pages 348–351 (1995)Cite this article

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.

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References

  1. Michail, J., Matsoukas, J. & Théodorou, S. Revue Chir. orthop. répar. Appar. moteur 43, 142–146 (1957).

    CAS  Google Scholar 

  2. Rubinstein, J. H. & Taybi, H. Am. J. Dis. Child. 105, 588–608 (1963).

    Article  CAS  Google Scholar 

  3. Hennekam, R. C. M., van den Boogaard, M. J., Sibbles, B. J. & van Spijker, H. G. Am. J. med. Genet. (Suppl.) 6, 17–19 (1990).

    CAS  Google Scholar 

  4. Imaizumi, K. & Koroki, Y. Am. J. med. Genet. 38, 636–639 (1991).

    Article  CAS  Google Scholar 

  5. Tommerup, N., van der Hagen, C. B. & Heiberg, A. Am. J. med. Genet. 44, 237–241 (1992).

    Article  CAS  Google Scholar 

  6. Lacombe, D., Saura, R., Taine, L. & Battin, J. Am. J. med. Genet. 44, 126–128 (1992).

    Article  CAS  Google Scholar 

  7. Breuning, M. H. et al. Am. J. hum. Genet. 52, 249–254 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Masuno, M. et al. Am. J. med. Genet. 53, 352–354 (1994).

    Article  CAS  Google Scholar 

  9. Chrivia, J. C. et al. Nature 365, 855–859 (1993).

    Article  ADS  CAS  Google Scholar 

  10. Hoeffler, J. P., Meyer, T. E., Yun, Y., Jameson, J. L. & Habener, J. F. Science 242, 1430–1432 (1988).

    Article  ADS  CAS  Google Scholar 

  11. Gonzales, G. A. et al. Nature 337, 749–752 (1989).

    Article  ADS  Google Scholar 

  12. Kwok, R. P. S. et al. Nature 370, 223–226 (1994).

    Article  ADS  CAS  Google Scholar 

  13. Roest, P. A. M., Roberts, R. G., Sugino, S., van Ommen, G. J. B. & den Dunnen, J. T. Hum. molec. Genet. 2, 1719–1721 (1993).

    Article  CAS  Google Scholar 

  14. Bird, A., Taggart, M., Frommer, M., Miller, O. J. & Macleod, D. Cell 40, 91–99 (1985).

    Article  CAS  Google Scholar 

  15. Lundblad, J. R., Kwok, R. P. S., Laurance, M. E., Harter, M. L. & Goodman, R. H. Nature 374, 85–88 (1995).

    Article  ADS  CAS  Google Scholar 

  16. Arany, Z., Newsome, D., Oldread, E., Livingston, D. M. & Eckner, E. Nature 374, 81–84 (1995).

    Article  ADS  CAS  Google Scholar 

  17. Eckner, R. E. et al. Genes Dev. 8, 869–884 (1994).

    Article  CAS  Google Scholar 

  18. Wessels, J. W. et al. Blood 77, 1555–1559 (1991).

    CAS  PubMed  Google Scholar 

  19. Tassabehji, M. et al. Nature Genet. 3, 26–30 (1993).

    Article  CAS  Google Scholar 

  20. Tassabehji, M. et al. Nature 355, 635–636 (1992).

    Article  ADS  CAS  Google Scholar 

  21. Hoth, C. F. et al. Am. J. hum. Genet. 52, 455–462 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Barr, F. G. et al. Nature Genet. 3, 113–117 (1993).

    Article  CAS  Google Scholar 

  23. Siraganian, P. A., Rubinstein, J. H. & Miller, R. W. Med. Pediatr. Oncol. 17, 485–491 (1989).

    Article  CAS  Google Scholar 

  24. Miller, R. W. & Rubinstein, J. H. Am. J. med. Genet. 56, 112–115 (1995).

    Article  CAS  Google Scholar 

  25. Gibbons, R. J., Picketts, D. J., Villard, L. & Higgs, D. R. Cell 80, 837–845 (1995).

    Article  CAS  Google Scholar 

  26. Dauwerse, J. G. et al. Blood 79, 1299–1304 (1992).

    CAS  PubMed  Google Scholar 

  27. Green, E. D. & Olson, M. V. Proc. natn. Acad. Sci. U.S.A. 87, 1213–1217 (1990).

    Article  ADS  CAS  Google Scholar 

  28. Parra, I. & Windle, B. Nature Genet. 5, 17–21 (1993).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Human Genetics, Leiden University, Sylvius Laboratories, Leiden, The Netherlands

    Fred Petrif, Rachel H. Giles, Hans G. Dauwerse, Jasper J. Saris, Gert-Jan B. van Ommen, Dorien J. M. Peters & Martijn H. Breuning

  2. Department of Human Genetics and Department of Pediatrics, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands

    Raoul C. M. Hennekam

  3. Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan

    Mitsuo Masuno

  4. Danish Centre for Human Genome Research, John F. Kennedy Institute, Glostrup, Denmark

    Niels Tommerup

  5. Department of Medical Genetics, Ullevaal University Hospital, Oslo, Norway

    Niels Tommerup

  6. Vollum Institute, Oregon Health Sciences University, Portland, Oregon, 97201, USA

    Richard H. Goodman

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  1. Fred Petrif
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Petrif, F., Giles, R., Dauwerse, H. et al. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376, 348–351 (1995). https://doi.org/10.1038/376348a0

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