New germline GATA1 variant in females with anemia and thrombocytopenia.

Abstract Familial forms of bone marrow defects are rare disorders and description of new cases are valuable opportunities to clarify the molecular machinery that triggers hematopoiesis and blood formation, as well as risk to malignant transformation. We propose to investigate the genetic scenario and possible patterns of familial transmission, by studying a rare case of familial myeloid disorder with a history of exposure to pesticides. Blood counts of two proband sisters revealed mild anemia, neutrophilia and thrombocytopenia with bone marrow finding mimicking primary myelofibrosis in the cellular phase. We analyzed 78 myeloid neoplasms-related genes and 16 encoding xenobiotic metabolizing genes of two sisters, age 41 and 42, previously diagnosed with myelofibrosis and thrombocytopenia. The GATA1 variant c.788C>T, p.T263M, located in the C-terminal zinc finger domain of GATA1, was detected in germline and somatic DNA of the two sisters. The screening of the other kindreds revealed the same variant in the mother and two daughters with the same bone marrow disorder. This is the first report of GATA1 variant in the CF domain causing anemia, thrombocytopenia and megakaryocyte proliferation with mild myelofibrosis, correlating a new GATA1 germline variant with myeloid disorder.