title: Evidence that expression of Sp alpha I/65 hereditary elliptocytosis is compounded by a genetic factor that is linked to the homologous alpha-spectrin allele.
abstract: Many cases of hereditary elliptocytosis (HE) result from mutated spectrin alpha-chains. It has repeatedly been observed that the amount of a mutant alpha-chain is different in various affected individuals, resulting in clinical pictures of variable severity. The different levels are thought to result from different percentages of the alpha-spectrin allele in trans. Such percentages, in turn, could be under genetic control. We tested this hypothesis in a large Algerian family with Sp alpha I/65 HE. In an informative sibship, we found three persons with a distinctly high level of expression of the Sp alpha I/65 variant, suggesting the existence, in trans, of a low percentage alpha-allele. The alpha-spectrin gene haplotype associated with the latter was constantly - + -, based on the XbaI, PvuII, and MspI polymorphic sites. In contrast, a basal level of expression of the Sp alpha I/65 variant in the same sibship indicated, in trans, the existence of a normal percentage alpha-allele. The haplotype corresponding to this other alpha-allele was + - +. Study of another generation of the family showed, however, that the - + - haplotype could also be linked to a normal percentage alpha-allele. These results are consistent with the view that the expression level of alpha I/65 spectrin (and of other types of alpha-variants) is compounded by a genetic factor that is linked to the normal alpha-allele in trans. The low percentage allele itself remains silent in the simple heterozygous state.
authors.affiliation: Centre Pierre et Marie Curie, CHU Mustapha, Alger, Algérie.
authors.forename: D
authors.initials: D
authors.lastname: Guetarni
authors.forename: A F
authors.initials: AF
authors.lastname: Roux
authors.forename: N
authors.initials: N
authors.lastname: Alloisio
authors.forename: F
authors.initials: F
authors.lastname: Morlé
authors.forename: M T
authors.initials: MT
authors.lastname: Ducluzeau
authors.forename: B G
authors.initials: BG
authors.lastname: Forget
authors.forename: P
authors.initials: P
authors.lastname: Colonna
authors.forename: J
authors.initials: J
authors.lastname: Delaunay
authors.forename: J
authors.initials: J
authors.lastname: Godet
mesh_terms: D004612:Elliptocytosis, Hereditary / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D013049:Spectrin / Q000235:genetics*
chemical_list: D013049:Spectrin