title: Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome).
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.
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
authors.forename: Valérie
authors.initials: V
authors.lastname: Proulle
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.forename: Samuel
authors.initials: S
authors.lastname: Bellais
authors.forename: Valérie
authors.initials: V
authors.lastname: Serre
authors.forename: Fatima
authors.initials: F
authors.lastname: Djouadi
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Capucine
authors.initials: C
authors.lastname: Vignon-Savoye
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: de Vernejoul
authors.forename: Laurence
authors.initials: L
authors.lastname: Legeai-Mallet
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Fischer
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Marie
authors.initials: M
authors.lastname: Dreyfus
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
mesh_terms: D019943:Amino Acid Substitution; D015519:Bone Density / Q000235:genetics; D001847:Bone Diseases / Q000097:blood / Q000235:genetics*; D016723:Bone Remodeling / Q000235:genetics; D020134:Catalytic Domain / Q000235:genetics; D002478:Cells, Cultured; D003241:Consanguinity; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D013577:Syndrome; D013928:Thromboxane A2 / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000097:blood / Q000235:genetics* / Q000502:physiology
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase