Haemolysates of family members from three generations, all of whom had polycythaemia, were analysed by polyacrylamide gel electrophoresis at pH 8.8. Two closely spaced major bands were observed, one of which corresponded to Hb A and the other to a new mutant designated Hb Vanderbilt. Whole blood from a heterozygote for Hb Vanderbilt was analysed for oxygen affinity which was found to be much higher than that of normal subjects. Haemoglobin Vanderbilt was separated from Hb A using anion exchange chromatography. Cation exchange chromatography yielded a variant beta chain from which a mutant peptide was identified with a structure corresponding to residues beta83--89 with a Ser leads to Arg replacement at position 89. The oxygen affinity of 'stripped' haemolysates from the heterozygote was found to be much less sensitive to added organic phosphates than haemolysates from normal subjects. In while blood, the decreased sensitivity to 2,3-diphosphoglycerate results in an increased oxygen affinity, thus explaining the clinical observations of tissue hypoxia and compensatory polycythaemia.

DOI: 10.1111/j.1365-2141.1978.tb01095.x
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