IDENTIFICATION OF A GENE INVOLVED IN HEREDITARY MICROCYTIC ANEMIA DUE TO DEFECTIVE IRON ABSORPTION IN A SARDINIAN FAMILY

Iron is a fundamental element to the organisms that live in an oxygen-rich environment. In fact, its capacity to accept and donate electrons makes it an essential oxygen-binding molecule, like hemoglobin, myoglobin and numerous enzymes. Iron balance is very weak and it is maintained by regulation of intestinal iron absorption because there is no regulated pathway for iron excretion. Iron absorption is modulated by the level of iron stores and by the amount of iron needed for erythropoiesis. In humans the greatest portion of total iron (65-75%) is found in hemoglobin in the red blood cells. Disorders iron homeostasis like iron deficiency and iron overload, are deleterious and can be hereditary or acquired. Iron overload can result from the increase catabolism of erythrocytes (transfusional iron overload) or from a hereditary tendency to absorb too much iron with very severe consequences on organs and tissues. In particular, hereditary hemochromatosis is a very frequent disease due to, in most cases, mutations in a recently identified gene, HFE. Iron deficiency, which results in microcytic anemia, usually is due to inadequate iron intake or excessive blood loss but can be associated with rare hereditary defects of iron absorption. Mutated genes that underlie this condition have not yet been identified in humans. With this project we intend to investigate a sardinian family with microcytic anemia refractary to oral iron treatment, with the purpose of detecting a gene most likely involved in iron absorption. Identification of the gene could give insights in iron metabolism which, although the remarkable progress of the past years, still remain poorly understood.