HB Coimbra or α2β299(Gl)ASP→GLU, A Newly Discovered High Oxygen Affinity Variant

We have identified a new high oxygen affinity hemoglobin variant in members of a Portuguese family; it is characterized by an Asp→Glu replacement at codon 99 of the β chain which is in the α1β2 interface. The altered functional properties of Hb Coimbra likely result from the inability to form a hydrogen bond between β99Glu and α42Tyr; such a bond is formed in deoxy Hb A between the normally occurring β99Asp and α42Tyr. The two affected members of the family have a distinct erythrocytosis with hemoglobin levels of 18 to 20 g/dl. The mutation in the β-globin gene (GAT→GAA at codon 99) resulting in the Asp→Glu replacement is the seventh type at this specific location. A review of the many variants of the α and β chains identifies primarily aspartic acid and glutatnic acid residues as being most frequently replaced; it is speculated that codons GAC and GAT (for Asp), and GAGand GAA (for Glu) are most susceptible to mutational events.