Chapter 9 Mutant Cytoskeletal Proteins in Hemolytic Disease

Abstract

Publisher Summary Changes in red cell shape in inherited hemolytic anemias known as “hereditary spherocytosis (HS) and hereditary elliptocytosis (HE),” from biconcave disc to spheres, ovalocytes, elliptocytes, and fragments, suggests missing or abnormal membrane components. HE has been shown to be the result of a variety of mutations in spectrin and protein 4.1, components of the erythrocyte cytoskeleton. Deficiency of ankyrin, component of the erythrocyte skeleton, has been shown to cause severe spherocytic hemolytic anemia. A recessive form of HS has been shown to be associated with a point mutation in the ninth repeat unit of the spectrin α subunit. The function of the cytoskeleton is to give the red cell the stability and deformability required for its passage, intact through the smallest capillaries of the circulatory system. Mutation of any cytoskeletal component that impairs its deformability and mechanical stability may significantly decrease red cell survival. This chapter discusses the detection and characterization of spectrin mutants in HE, mutant forms of protein 4.1 in HE, and HS. HS and HE may be the result of inadequate production of or mutations and deletions in spectrin, ankyrin, and protein 4.1. It is possible that deficiencies or mutations of less abundant skeletal proteins, for example 4.2 and 4.9, may also cause abnormal red cell shape and life span. It can be speculated that mutational events in transmembrane proteins may be responsible for changes in the red cell volume, shape, and survival, as observed in stomatocytosis, and the rarer disorders of cell volume known as “dessicocytosis and xerocytosis.” Characterization of the mutant red cell membrane proteins, causing hemolytic states, has enhanced the understanding of the structure and function of the normal erythrocyte cytoskeleton.