NON-MUSCLE MYOSIN IIA: FROM GENE MUTATIONS TO ILLNESSES

May-Hegglin anomaly (MHA), Sebastian platelet syndrome (SBS), Fechtner syndrome (FTNS) and Epstein syndrome (EPTS) are hereditary disorders characterized from birth by a bleeding tendency deriving from thrombocytopenia. An additional feature of these disorders is the presence of giant platelets. Patients with FTNS and EPTS during ageing develop also a nephropathy that slowly progresses to end-stage renal failure and often requires dialysis or kidney transplantation. In addition, they often develop a progressive sensorineural hearing loss and sometimes cataract. At the opposite, patients with MHA or SBS suffer during their lifetime from thrombocytopenia only. Diagnosis of these illnesses is difficult and troublesome for the patient because it often requires bone marrow and/or kidney biopsy. Moreover, at birth it in not possible to distinguish MHA and SBS from FTNS-EPTS and to know which patients will develop defects of kidney, hearing and viewing. Investigations performed during the year 2000 demonstrated that MHA, SBS, FTNS and EPTS derive from mutations of a single gene coding for a contractile protein (non-muscle myosin IIA). At present it is therefore possible to diagnose theses illnesses by a simple drawing of peripheral blood and by the study of the involved gene. However, it is still impossible to know if one single patient will suffer in the future only from thrombocytopenia or will develop nephropathy, hearing loss and cataract too. The aim of the proposed research is to understand the mechanism by which different mutations of the same gene may induce defects of platelets, kidney, hearing and viewing. If our study will reach this goal, it will be possible at birth to anticipate the natural history of the illness in each single patient and to adopt preemptive and therapeutic measures.