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Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome)

Nature Genetics volume 40, pages 284–286 (2008)Cite this article

Abstract

Studying consanguineous families with Ghosal hematodiaphyseal dysplasia syndrome (GHDD), a disorder of increased bone density, we identified mutations in TBXAS1, which encodes thromboxane synthase (TXAS). TXAS, an enzyme of the arachidonic acid cascade, produces thromboxane A2 (TXA2). Platelets from subjects with GHDD showed a specific deficit in arachidonic acid–produced aggregation. We also found that TXAS and TXA2 modulated expression of TNFSF11 and TNFRSF11B (encoding RANKL and osteoprotegerin (OPG), respectively) in primary cultured osteoblasts.

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Figure 1: TXAS and TXA2 modulate the TNFSF11 pathway.
Figure 2: Platelet studies.

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References

  1. Ghosal, S.P., Mukherjee, A.K., Mukherjee, D. & Ghosh, A.K. J. Pediatr. 113, 49–57 (1988).

    Article  CAS  Google Scholar 

  2. Isidor, B. et al. Hum. Genet. 121, 269–273 (2007).

    Article  CAS  Google Scholar 

  3. Mestel, F. et al. Lancet 1, 157 (1980).

    Article  CAS  Google Scholar 

  4. Weiss, H.J. & Lages, B.A. Lancet 1, 760–761 (1977).

    Article  CAS  Google Scholar 

  5. Gruber, R., Karreth, F., Fischer, M.B. & Watzek, G. Bone 30, 726–732 (2002).

    Article  CAS  Google Scholar 

  6. Shen, R.F. & Tai, H.H. J. Biomed. Sci. 5, 153–172 (1998).

    Article  CAS  Google Scholar 

  7. Hsu, P.Y., Tsai, A.L. & Wang, L.H. Arch. Biochem. Biophys. 383, 119–127 (2000).

    Article  CAS  Google Scholar 

  8. Yu, I.S. et al. Blood 104, 135–142 (2004).

    Article  CAS  Google Scholar 

  9. Davies, P., Bailey, P.J., Goldenberg, M.M. & Ford-Hutchinson, A.W. Annu. Rev. Immunol. 2, 335–357 (1984).

    Article  CAS  Google Scholar 

  10. Taniguchi, S., Shibuya, T., Harada, M. & Niho, Y. Kidney Int. 36, 712–718 (1989).

    Article  CAS  Google Scholar 

  11. Pilbeam, C.C., Harrison, J.R. & Raisz, L.G. Principle of Bone Biology 2nd edn. Ch. 54 (Academic, New York, 2002).

    Google Scholar 

  12. Raisz, L.G. & Woodiel, F.N. Prostaglandins Other Lipid Mediat. 71, 287–292 (2003).

    Article  CAS  Google Scholar 

  13. Jorgensen, H.R., Svanholm, H. & Host, A. Acta Orthop. Scand. 4, 464–466 (1988).

    Article  Google Scholar 

  14. Ralston, S.H. & de Crombrugghe, B. Genes Dev. 20, 2492–2506 (2006).

    Article  CAS  Google Scholar 

  15. Watkins, B.A., Lippman, H.E., Le Bouteiller, L., Li, Y. & Seifert, M.F. Prog. Lipid Res. 40, 125–148 (2001).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the subjects and their families for their support. We thank D. Rabier, M. Dechaux and O. Boccara from the Necker-Enfants Malades Hospital for technical support and D. Renier from the Necker-Enfants Malades Hospital for providing normal cranial sutures.

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Authors and Affiliations

  1. Département de Génétique, Unité INSERM U781, Université Paris Descartes, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker-Enfants Malades, 149, rue de Sèvres, Paris, 75015, France

    David Geneviève, Bertrand Isidor, Samuel Bellais, Valérie Serre, Laurence Legeai-Mallet, Martine Le Merrer, Arnold Munnich & Valérie Cormier-Daire

  2. AP-HP, Laboratoire d'Hématologie, Université Paris-Sud, Hôpital Kremlin-Bicêtre, 78 rue du Général Leclerc, Kremlin Bicêtre, 94275, France

    Valérie Proulle & Marie Dreyfus

  3. Centre National de la Recherche Scientifique UPR9078, Hôpital Necker Enfants Malades, 149, rue de Sèvres, Paris, 75015, France

    Fatima Djouadi

  4. AP-HP, Unité d'Immuno-Hématologie et de Rhumatologie Pédiatrique, Hôpital Necker Enfants Malades, 149, rue de Sèvres, Paris, 75015, France

    Capucine Picard & Stéphane Blanche

  5. Service de Pédiatrie, Centre Hospitalier Intercommunal Le Raincy-Montfermeil, 10 rue du Général Leclerc, Montfermeil, 93370, France

    Capucine Vignon-Savoye

  6. AP-HP, Service d'Hématologie Pédiatrique, Hôpital Robert Debré, 48 boulevard Sérurier, Paris, 75019, France

    Brigitte Bader-Meunier

  7. Département de Rhumatologie, AP-HP, Hôpital Lariboisière, Paris, 2 rue Ambroise Paré, Paris, 75010, France

    Marie-Christine de Vernejoul

  8. AP-HP, Laboratoire d'Hématologie, Hôpital Européen Georges Pompidou, 20 rue Leblanc, Paris, 75015, France

    Anne-Marie Fischer & Pascale Gaussem

Authors
  1. David Geneviève
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  18. Valérie Cormier-Daire
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Contributions

D.G. and B.I. performed the sequence analysis; V.P. and M.D. performed the platelet exocytosis studies; V.S. performed the three-dimensional modeling of TXAS; D.G. and F.D. performed the real-time quantitative PCR analysis; C.P., C.V.-S., B.B.-M., S. Blanche, M.-C.d.V., M.L.M. and V.C.-D. provided clinical data; D.G., S. Bellaris and L.L.-M. performed primary osteoblast cultures; A.-M.F. and P.G. performed the platelet aggregation studies; D.G. and S. Bellaris performed the ELISA; and D.G., A.M. and V.C.-D. designed the experiment and wrote the manuscript.

Corresponding author

Correspondence to Valérie Cormier-Daire.

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Supplementary Figures 1–4, Supplementary Tables 1–2, Supplementary Methods (PDF 1746 kb)

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Geneviève, D., Proulle, V., Isidor, B. et al. Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome). Nat Genet 40, 284–286 (2008). https://doi.org/10.1038/ng.2007.66

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