A new gene for inherited thrombocytopenias: clinical, pathogenetic and pharmacological studies

A reduced blood platelet count since birth characterizes a number of genetic disorders named inherited thrombocytopenias. In severe forms patients present recurrent spontaneous bleedings, while in mild cases haemorrhages occur on the occasion of surgery, delivery or trauma. Making a definite diagnosis of these disorders is often difficult, because complex laboratory tests are required. Moreover, in nearly 50% of patients it is even impossible, because their illnesses have never been described. Not only diagnostic, but also therapeutic skills for inherited thrombocytopenias are limited, since no drug to stably increase platelet count is available and the only treatment to achieve this goal is bone marrow transplantation. However, this procedure exposes to the risk of harmful side effects and requires a compatible donor. This project aims at improving both diagnosis and therapy of these disorders by unravelling a new form and identifying drugs that could be used to increase platelet count in affected patients. Examining a limited number of patients with an inherited thrombocytopenia of unknown origin, we obtained quite recently strong evidences suggesting that about 25% of them have mutations in a gene that has never been implicated in this type of disorders. We are now planning to confirm these preliminary results extending our study to a larger case series of patients. Since we expect to identify several, additional families with this new disorder, we will able to characterize all the aspects of the illness by their clinical and laboratory investigation. Concerning therapy, based on the positive results we are obtaining with a new drug in another form of inherited of thrombocytopenia, we are confident of identifying by in vitro experiments one or more substances that are effective in increasing platelet count also in the new condition.