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

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. [ABSTRACT FROM AUTHOR]