Defective spectrin dimer–dimer association in a family with transfusion dependent homozygous hereditary elliptocytosis

Abstract

Red cell membrane proteins have been examined in a family in which three children have severe transfusion-dependent homozygous hereditary elliptocytosis. The membranes in all three show a considerable excess of spectrin dimers over tetramers in spectrin extracts. The red cell membranes of their parents with heterozygous hereditary elliptocytosis show a lesser but significant increase in spectrin dimers. Some of the family members also have an alpha-globin gene deletion and haemoglobin D trait. The present results are the first demonstration of a defect of spectrin dimer-dimer association in homozygous elliptocytosis and provide strong support for the concept that this defect is the primary cause of the red cell abnormality in at least some families of hereditary elliptocytosis.