title: Unique alpha-spectrin mutant in a kindred with common hereditary elliptocytosis.
abstract: We report here a unique variant of alpha spectrin in a kindred with hereditary elliptocytosis. This novel red blood cell-membrane protein migrated to a position between the normal alpha- and beta-spectrin subunits in SDS polyacrylamide gel electrophoresis. It was identified as an alpha spectrin by its binding to anti-alpha spectrin antibodies, by the absence of a phosphorylation site, and by the normal 1:1 stoichiometry between total alpha- and beta-spectrin molecules. The quantity of the alpha-spectrin mutant, expressed as a percentage of the total alpha spectrin, varied from 9.9-45.2% among six affected individuals. Two-dimensional electrophoretic analysis of spectrin tryptic digests was qualitatively normal but showed a decreased quantity of a normal alpha IV fragment. The variable quantity of alpha-spectrin mutant among family members correlated directly with the increased percentage of spectrin dimers in cold low ionic strength spectrin extracts (r = 0.92) and inversely with red blood cell ghost mechanical stability (r = -0.98). The data suggest that this new alpha-spectrin mutant is responsible for decreased spectrin dimer-dimer association and for red cell instability in affected individuals.
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D004612:Elliptocytosis, Hereditary / Q000097:blood / Q000235:genetics*; D004910:Erythrocyte Membrane / Q000032:analysis / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D007159:Immunologic Tests; D007223:Infant; D046911:Macromolecular Substances; D008297:Male; D009154:Mutation; D009994:Osmolar Concentration; D010375:Pedigree; D010766:Phosphorylation; D013049:Spectrin / Q000235:genetics* / Q000378:metabolism; D013314:Stress, Mechanical; D014357:Trypsin / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances; D013049:Spectrin; D014357:Trypsin