Hemoglobin Brigham (α2(A)β2(100 Pro → Leu)). Hemoglobin variant associated with familial erythrocytosis

Abstract

Erythrocytosis associated with the presence of a hemoglobin with increased oxygen affinity is reported for 10 hemoglobin variants, most of which demonstrate altered electrophoretic mobility. Several members of a family were found to have erythrocytosis, and both the whole blood and the hemoglobin exhibited increased oxygen affinity. Phosphate free hemoglobin solutions had a normal Bohr effect and reactivity to 2,3 diphosphoglycerate. The electrophoretic properties of the hemoglobin were normal, but on peptide mapping of a tryptic digest of the isolated β chains, a normal βT11 peptide and an abnormal βT11 with greater R(f) were seen. Analysis of the abnormal peptide showed the substitution of leucine for the normal proline at β100 (helical residue G2). The hemoglobin variant, designated Hb Brigham, serves to emphasize the necessity for detailed evaluation of the structure and function of hemoglobin in familial erythrocytosis even with electrophoretically 'normal' hemoglobin.