Hemoglobin Crete ( fi 129 Ala - k Pro ) : A New High - Affinity Variant Interacting With $ # { 176 } -

Hemoglobin Crete, 1 29 (H7) ala -k pro, is #{149} new mutant hemoglobin (Hb) with high oxygen affinity that was discovered in a Greek family in various combinations with #{176}and #{244} ’-thaIassemia. The propositus. who presented an unusual clinical picture of an “overcompenseted” hemolytic state. with erythrocytosis. splenomegaly. abnormal red cell morphology, and marked erythroid hyperplasia. appeared doubly heterozygous for Hb Crete and 8#{176}-thalassemia. His red cells contained 87% Hb Crete and 30% Hb F, and the combination of these two hemoglobins resulted in a blood P o2 of 11.2 mm Hg. A brother with Hb Crete trait (38% Hb Crete, 56% Hb A. blood Pee02 23.0 mm Hg) did not have significant erythrocytosis. Purified Hb Crete was heat-unstable and exhibited a high oxygen affinity, moderately decreased cooperativity, and a normal Bohr effect. We postulate that the 1 29 proline substitution disrupts the H helix, perturbing nearby residues involved in a1 , contact sites of the Hb tetramer.