Brief Communication abstract
Nature Genetics 40, 284 - 286 (2008)
Published online: 10 February 2008 | doi:10.1038/ng.2007.66
Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome)
David Geneviève1, Valérie Proulle2, Bertrand Isidor1, Samuel Bellais1, Valérie Serre1, Fatima Djouadi3, Capucine Picard4, Capucine Vignon-Savoye5, Brigitte Bader-Meunier6, Stéphane Blanche4, Marie-Christine de Vernejoul7, Laurence Legeai-Mallet1, Anne-Marie Fischer8, Martine Le Merrer1, Marie Dreyfus2, Pascale Gaussem8, Arnold Munnich1 & Valérie Cormier-Daire1
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.
- 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.
- AP-HP, Laboratoire d'Hématologie, Université Paris-Sud, Hôpital Kremlin-Bicêtre, 78 rue du Général Leclerc, 94275 Kremlin Bicêtre, France.
- Centre National de la Recherche Scientifique UPR9078, Hôpital Necker Enfants Malades, 149, rue de Sèvres, 75015 Paris, France.
- AP-HP, Unité d'Immuno-Hématologie et de Rhumatologie Pédiatrique, Hôpital Necker Enfants Malades, 149, rue de Sèvres, 75015 Paris, France.
- Service de Pédiatrie, Centre Hospitalier Intercommunal Le Raincy-Montfermeil, 10 rue du Général Leclerc, 93370 Montfermeil, France.
- AP-HP, Service d'Hématologie Pédiatrique, Hôpital Robert Debré, 48 boulevard Sérurier, 75019 Paris, France.
- AP-HP, Département de Rhumatologie, Hôpital Lariboisière, Paris, 2 rue Ambroise Paré, 75010 Paris, France.
- AP-HP, Laboratoire d'Hématologie, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France.
Correspondence to: Valérie Cormier-Daire1 e-mail: cormier@necker.fr
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