Molecular basis of spectrin deficiency in hereditary pyropoikilocytosis. Blood

Hereditary pyropoikilocytosis (HPP) is a recessively in-herited hemolytic anemia characterized by severe poikilo-cytosis and red blood cell fragmentation. HPP red blood cells are partially deficient in spectrin and contain a mutant a or j3-spectrin that is defective in terms of spectrin self-as-sociation. Although the nature of the latter defect has been studied in considerable detail and many mutations of a-spectrin and B spectrin have been identified, the molecular basis of spectrin deficiency is unknown. Here we report two mechanisms underlying spectrin deficiency in HPP. The first mechanism involves a thalassemia-like defect characterized by a reduced synthesis of a-spectrin as shown by studies involving synthesis of spectrin in two unrelated HPP probands and their parents: One parent car-ries the elliptocytogenic spectrin mutation, whereas th