title: Spectrin alpha IIa variant in dominant and non-dominant spherocytosis.
abstract: Several polymorphic mutations are located on the spectrin alpha-chain; among these the variant termed alpha IIa is characterized by an acid shift in the isoelectric point of the tryptic digest peptides 46 kDa and 35 kDa. In this variant a single amino acid substitution (alanine to aspartic acid) occurred at position 972 of the spectrin alpha-chain due to a point mutation (GCT to GAT) in the DNA. This variant, which seemed 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 alpha IIa variant by denaturing electrophoresis of the spectrin tryptic digest peptides from 179 subjects: 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 chromosome bearing the alpha IIa 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 gene(s) were located on different chromosomes and inherited independently from each other. Furthermore, our study allows the conclusion that in most (if not all) cases of dHS, the alpha IIa the variant is not the cause, is not a marker, and does not influence the phenotypic expression of the disease.
authors.affiliation: INSERM U.160, Hôpital Beaujon, France.
authors.forename: P
authors.initials: P
authors.lastname: Boivin
authors.forename: C
authors.initials: C
authors.lastname: Galand
authors.forename: I
authors.initials: I
authors.lastname: Devaux
authors.forename: M C
authors.initials: MC
authors.lastname: Lecomte
authors.forename: M
authors.initials: M
authors.lastname: Garbarz
authors.forename: D
authors.initials: D
authors.lastname: Dhermy
mesh_terms: D000328:Adult; D000409:Alanine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D001483:Base Sequence; D002648:Child; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013049:Spectrin / Q000235:genetics*; D013103:Spherocytosis, Hereditary / Q000235:genetics*
chemical_list: D013049:Spectrin; D001224:Aspartic Acid; D000409:Alanine