Abnormal electrophoretic mobility of spectrin tetramers in hereditary elliptocytosis.
Hereditary elliptocytosis (HE) is a genetically determined disorder of the red cell membrane. The main protein which composes the proteinaceous skeleton of the membrane is an elongated molecule named spectrin which is a heterodimer composed of two chains, alpha and beta. In the membrane spectrin dimers are associated head-to-head to form tetrameric structures. We and other authors have reported that spectrin studied from many HE patients exhibited a dimer self-association defect (type I HE). A mutation in the head of the spectrin alpha chain was mostly found in type I HE. We have previously described one of the three known spectrin pathological variants shown on mild tryptic digest pattern. This variant was characterized by the appearance of an abnormal 65,000-dalton peptide (Sp alpha I/65). Using nondenaturating gel electrophoresis, we describe in this paper a triplicated pattern of the spectrin tetramer bands which is found in heterozygous HE cases displaying the 65,000-dalton variant. Study of a homozygous case allowed us to characterize the electrophoretic mobility of the abnormal symmetrical spectrin tetramer (alpha 2I/65-beta 2) and to study the correlation between the fraction of this abnormal symmetrical tetramer found in heterozygous patients and the amount of the 65,000-dalton peptide observed in spectrin tryptic digests.
D004591:Electrophoresis, Polyacrylamide Gel; D004612:Elliptocytosis, Hereditary / Q000097:blood*; D004910:Erythrocyte Membrane / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008970:Molecular Weight; D013049:Spectrin / Q000032:analysis* / Q000235:genetics
D013049:Spectrin