Hereditary elliptocytosis (HE) is a group of hemolytic anemias characterized by the presence of elliptical erythrocytes. The underlying alterations lie in the proteins of the membrane skeleton. Defects of the αI domain of spectrin have been defined based on a decrease in the normal 80-kD αI domain and a concomitant increase in one or more lower molecular weight peptides. We have studied three Brazilian kindreds with black ancestry, who presented mild common spαI/50 HE. Our aim was to determine the molecular alteration responsible for the spαI/50 HE observed in these three kindreds and to evaluate the presence and influence of allele αLELY in the expression of this type of HE. In order to establish the molecular defect, exons 5, 6 and 11 were amplified and submitted to a nonradioactive single strand conformation polymorphism protocol. An identical band shift in exon 6 was observed in all 3 patients and their affected relatives. Direct sequencing of the amplification products of exon 6 showed the same molecular defect in all patients: a T→C substitution, responsible for the L260P mutation. Allele αLELY, detected by PCR and restriction enzyme digestion, was present in the heterozygous form in the three propositi and was associated in trans with the elliptocytogenic mutation. Blood smears of the patients with HE and αLELY in trans showed pronounced elliptocytosis, poikilocytosis and a few small red cell fragments, whereas the blood smears of their relatives, who had HE without allele αLELY, showed mild common HE with a predominance of ovalocytes and the absence of poikilocytes. We conclude that allele αLELY does not lead to the worsening of clinical conditions when associated in trans with mild HE, but can be easily distinguished by a blood smear analysis. The predominance of the L260P mutation in the kindreds studied could be related to the colonization of Brazil during the slave trade by Africans from the Benin-Togo area, where this mutation is particularly common.

Keywords:
Hereditary elliptocytosis, Erythrocyte membrane, α-Spectrin, Allele αLELY, Brazilian population
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