SPECTRIN ALPHA-IIA VARIANT IN DOMINANT AND NONDOMINANT SPHEROCYTOSIS

Several polymorphic mutations are located on the spectrin alpha-chain; among these the variant termed alphaIIa is characterized by an acid s hift in the isoelectric point of the tryptic digest peptides 46 kDa an d 35 kDa. In this variant a single amino acid substitution (alanine to aspartic acid) occured at position 972 of the spectrin alpha-chain du e to a point mutation (GCT to GAT) in the DNA. This variant, which see med very rare in normal people, could be related to the recessive form of hereditary spherocytosis (HS) and could be absent in the dominant form of the disease. We have studied the alphaIIa variant by denaturin g electrophoresis of the spectrin tryptic digest peptides from 179 sub jects: 46 controls, 78 patients with dominant (d) or non-dominant (nd) HS and 55 relatives of the patients. The confirmation of the results was obtained at the DNA level in 41 subjects. The frequency of the chr omosome bearing the alphaIIa mutation was 7.6% in controls and higher (about 12-14%) in members of families with dHS as well ndHS. However, the family trees clearly showed that the mutation and the HS disease g ene(s) were located on different chromosomes and inherited independent ly from each other. Furthermore, our study allows the conclusion that in most (if not all) cases of dHS, the alphaIIa the variant is not the cause, is not a marker, and does not influence the phenotypic express ion of the disease.