ROLE OF NON MUSCLE MYOSIN IIA IN MYH9 RELATED DISEASE

The term “MYH9 related disease” (MYH9RD) indicates a group a four diseases known as May-Hegglin anomalies, Sebastian, Fetchner, and Epstein syndromes. At birth, patients present macrothrombocytopenia (low platelet number and increased platelet volume) that might cause severe hemorrhages, and leukocyte inclusions; during life they can develop deafness, cataract and nephritis that can lead to dialysis and transplantation for renal failure. They are autosomal dominant diseases due to mutations in MYH9, the gene encoding for the non-muscle myosin heavy chain IIA. Although the functional role of this protein is not clear, it plays an important role in many cellular functions, such as citokinesis, shape change, and movement. In addition, since MYH9RD includes rare diseases that have been neglected in the past by the scientific community, we lack of knowledge not only on molecular mechanisms responsible for the disease but also on many clinical and therapeutic aspects. The aim of this project is, therefore, to develop different research areas leading to (1) accurate evaluation of clinical and diagnostic aspects to identify affected individuals and establish who is at risk to develop the most severe haematological and renal manifestations; (2) development of cellular and animal experimental systems in order to understand the function of myosin IIA and how mutations cause the disease. Our study will also test the effect of drugs that are currently used for similar disorders and that could be useful also in MYH9RD patients to ameliorate bleeding tendency and postpone or prevent the kidney disease. Of note, knowledge on basic molecular mechanisms might lead to the development of novel therapeutic strategies.