rs33927093

This review comprehensively surveys over 200 hemoglobin variants with high oxygen affinity reported since 1966. Approximately one-third of these variants cause compensatory erythrocytosis (polycythemia), with severity depending on the molecular defect. The paper explains the molecular mechanisms (alterations in R/T state equilibrium, 2,3-DPG binding, and Bohr effect), clinical presentation, diagnosis through oxygen dissociation curve measurement, and treatment approaches.

A case report of Hemoglobin Puttelange, a novel de novo hemoglobin variant caused by an alanine-to-valine substitution at β-globin position 140, identified in two siblings with polycythemia. The mutation displayed increased oxygen affinity (P50 = 16 mmHg vs normal 27 mmHg) and evidence of germline mosaicism in the father, indicating potential recurrence risk.