geographical micro mapping clinical and molecular profiling of patients with beta thalassemia major from tamilnadu

Abstract

newline Beta (and#946;) thalassemia is an inherited disorder of hemoglobin synthesis 1,2. In beta thalassemia there is a quantitative reduction in and#946; globin chain production of the hemoglobin tetramer. Mutations that completely inactivate the HBB gene result in almost no and#946; globin production and it causes a severe form of thalassemia called and#946;0 thalassemia. Mutations which allow for partial production of and#946; chains results in an attenuated form called and#946;+ thalassemia. A quantitative reduction in and#946; chains results in accumulation of excess alpha globin chains that results in the formation of insoluble aggregates leading to denaturation and degradation of these chains and finally forms insoluble precipitates. These insoluble precipitates and hemichromes induce reactive oxygen radicals which causes red cell membrane damage. Membrane damage leads to ineffective hematopoiesis within the bone marrow, hemolysis of cells within the circulation, stimulates binding of immunoglobulins and complements to the red cells thereby triggering the loss of red cells in the spleen resulting in anemia 1,2. This leads to reduced tissue oxygenation and increase erythropoietin levels and over stimulation of the bone marrow. Bone marrow expansion then causes skeletal deformities and osteopenia. Substances released from the degenerating red cell