2. Academic Validation
  3. Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome)

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

  • Nat Genet. 2008 Mar;40(3):284-6. doi: 10.1038/ng.2007.66.
David Geneviève 1,  Valérie Proulle,  Bertrand Isidor,  Samuel Bellais,  Valérie Serre,  Fatima Djouadi,  Capucine Picard,  Capucine Vignon-Savoye,  Brigitte Bader-Meunier,  Stéphane Blanche,  Marie-Christine de Vernejoul,  Laurence Legeai-Mallet,  Anne-Marie Fischer,  Martine Le Merrer,  Marie Dreyfus,  Pascale Gaussem,  Arnold Munnich,  Valérie Cormier-Daire
Affiliations

Affiliation

  • 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, 75015 Paris, France.
PMID: 18264100 DOI: 10.1038/ng.2007.66
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 A(2) (TXA(2)). Platelets from subjects with GHDD showed a specific deficit in arachidonic acid-produced aggregation. We also found that TXAS and TXA(2) modulated expression of TNFSF11 and TNFRSF11B (encoding RANKL and Osteoprotegerin (OPG), respectively) in primary cultured osteoblasts.

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