title: Hb Coimbra or alpha 2 beta (2)99(G1)Asp----Glu, a newly discovered highoxygen affinity variant.
abstract: 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 beta chain which is in the alpha 1 beta 2 interface. The altered functional properties of Hb Coimbra likely result from the inability to form a hydrogen bond between beta 99Glu and alpha 42Tyr; such a bond is formed in deoxy Hb A between the normally occurring beta 99Asp and alpha 42Tyr. The two affected members of the family have a distinct erythrocytosis with hemoglobin levels of 18 to 20 g/dl. The mutation in the beta-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 alpha and beta chains identifies primarily aspartic acid and glutamic acid residues as being most frequently replaced; it is speculated that codons GAC and GAT (for Asp), and GAG and GAA (for Glu) are most susceptible to mutational events.
authors.affiliation: Department of Hematology Centro Hospitalier de Coimbra, Portugal.
authors.forename: G P
authors.initials: GP
authors.lastname: Tamagnini
authors.forename: M L
authors.initials: ML
authors.lastname: Ribeiro
authors.forename: V
authors.initials: V
authors.lastname: Valente
authors.forename: M
authors.initials: M
authors.lastname: Ramachandran
authors.forename: J B
authors.initials: JB
authors.lastname: Wilson
authors.forename: E
authors.initials: E
authors.lastname: Baysal
authors.forename: L H
authors.initials: LH
authors.lastname: Gu
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D003062:Codon; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism; D010108:Oxyhemoglobins / Q000378:metabolism; D010449:Peptide Mapping; D011086:Polycythemia / Q000097:blood / Q000235:genetics*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; D010108:Oxyhemoglobins; C074593:hemoglobin Coimbra; D005914:Globins; D010100:Oxygen