Hb Aghia Sophia [α62(E11)Val→0 (α1)], an “In-Frame” Deletion Causing α-Thalassemia

Abstract

In this report we describe a case of Hb H disease due to the interaction of the -^(MEDI) deletion with a new (α⁺-thalassemia determinant. The molecular analysis of the proband's genomic DNA was carried out by polymerase chain reaction amplification and sequencing of both α genes of the α⁺-thalassemia chromosome and revealed a deletion of codon 62 of the α1 gene. This DNA triplet codes for a valine residue at the E11 α helix, which is located in the interior of the heme pocket. Substitutions of valine E11 with other amino acid residues in the α as well as β polypeptide chains lead, in the heterozygous carrier, either to Hb M disease or to congenital non-spherocytic hemolytic anemia. We assume that the deletion of valine at α62(E11) disrupts the conformation of the α chain to such an extent that the mutated subunit is rapidly removed by proteolysis. The final result is an α-thalassemia phenotype rather than an unstable hemoglobin syndrome. This conclusion is supported by the apparent absence of an abnormal α chain in the peripheral blood of the patient.