Hemoglobinopathic Erythrocytosis due to a New Electrophoretically Silent Variant, Hemoglobin San Diego (β109(G11)Val→Met)

Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.

“…Because these mutant hemoglobins have increased affinity for oxygen, the release of oxygen to tissues is impaired, and secondary erythrocytosis ensues. About one third of these variants are electrophoretically silent (2)(3)(4)(5)(6). Accordingly, the diagnosis must be established by the demonstration of a "shift to the left" of the oxygen dissociation curve.…”

Hemoglobin San Diego (β109 (G11) Val→Met) CRYSTAL STRUCTURE OF THE DEOXY FORM

“…The inseparable or electrophoretically silent hemoglobin mutants are difficult to characterize by chemical methods, as shown by Nute, Stamatoyannopoulos, Hermodson, and Roth (1) in the accompanying paper. Xray analysis is a physical method which allows the three-dimensional structure of a protein to be determined without any knowledge of its chemical constitution (though not all amino acid side chains can be identified).…”

Haemoglobinopathies with high oxygen affinity. Experience of Erythropathology Cooperative Spanish Group

“…Mutations experienced by amino acids enclosed in these zones, which are critical for haemoglobin functions, can therefore determine alterations in affinity to oxygen [11]. Of the ten high-affinity haemoglobinopathies found by our laboratory, in four (Hb San Diego, Hb Johnstown, Hb Malmö and Hb Columbia-Missouri), the amino acid change affects the α 1 β 2 contact zones [12][13][14][15], while in two (Hb Strasbourg and Hb Syracuse) the bonds to 2,3-DPG, in the central cavity, are affected [16,17], and in another two (Hb Badalona and Hb La Coruña) the contact cavity to the haem group [18,19] is affected and in one (Hb Bethesda) the α 1 β 1 contact zone is affected [20]. But, in the Hb Olympia, the amino acid change is located in site 20 of the chain helix B and there is no relation to any of the aforementioned zones, but it is accompanied by erythrocytosis.…”