Geneviève David, Proulle Valérie, Isidor Bertrand, Bellais Samuel, Serre Valérie, Djouadi Fatima, Picard Capucine, Vignon-Savoye Capucine, Bader-Meunier Brigitte, Blanche Stéphane, de Vernejoul Marie-Christine, Legeai-Mallet Laurence, Fischer Anne-Marie, Le Merrer Martine, Dreyfus Marie, Gaussem Pascale, Munnich Arnold, Cormier-Daire Valérie
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.
Nat Genet. 2008 Mar;40(3):284-6. doi: 10.1038/ng.2007.66. Epub 2008 Feb 10.
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.
在研究患有戈萨尔血骨干发育异常综合征（GHDD，一种骨密度增加的疾病）的近亲家庭时，我们在编码血栓素合酶（TXAS）的TBXAS1中发现了突变。TXAS是花生四烯酸级联反应中的一种酶，可产生血栓素A2（TXA2）。患有GHDD的受试者的血小板在花生四烯酸诱导的聚集方面表现出特定缺陷。我们还发现，TXAS和TXA2在原代培养的成骨细胞中调节TNFSF11和TNFRSF11B（分别编码RANKL和骨保护素（OPG））的表达。
