An α-spectrin mutation responsible for hereditary elliptocytosis associated in cis with the αV/41 polymorphism

The α207 Leu→Pro mutation in spectrin has recently been identified as a cause of αI/50-46a hereditary elliptocytosis (HE) or pyropoikilocytosis among Black people. We have found this mutation in a Moroccan family in both the heterozygous and homozygous states. The mutated α-spectrin allele carried, in cis, the αV/41 polymorphism, a common polymorphism altering the peptide maps and associated with a low-expression level. This is the first report of the cis combination of an HE mutation and the αV/41 polymorphism. Presumably, such a combination accounts for the very low expression of the abnormal allele in the heterozygous state.