Hereditary Spherocytosis With Spectrin Deficiency Due to an Unstable Truncated p Spectrin

Red cell membrane protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and direct quantitation by radioimmunoassay or cytofluorometry defines four distinct subsets of patients with hereditary spherocytosis: Patients with isolated spectrin deficiency, combined spectrin and ankyrin deficiency, band 3 deficiency, and protein 4.2 deficiency. In regard to the first group, only one mutation of p spectrin has been reported in the literature. We describe a spectrin variant characterized by a truncated p chain, and associated with hereditary spherocytosis and isolated spectrin deficiency. The clinical phenotype consists of a moderate hemolytic anemia with spherocytosis and frequent spiculation of the red cells. We present the biochemical characteristics of this mutant protein a d show that it constitutes only 12% of the total spectrin on the membrane. We show that the truncation of the protein is the