title: Hemoglobins with high oxygen affinity leading to erythrocytosis. New variants and new concepts.
abstract: This review brings some new insights on erythrocytosis of genetic origin related to problems of oxygen delivery by hemoglobin (Hb). A few molecular mechanisms are individualized among the about 100 Hb variants that cause compensatory erythrocytosis. The most frequently observed structural modifications are localized in the alpha1beta2 interface, or at the C-terminal. They impair formation of a stable T state. Others mutations modify directly or indirectly the surrounding of the heme and the site where oxygen binds. A special interest is brought to the dose effect considering the possibility for formation of hybrid tetramers with altered oxygen binding properties. Homozygous cases, and patients who are compound heterozygotes for a high oxygen affinity Hb and a thalassemia (thal), are discussed. Several examples are provided, specially documented for Hb Olympia [beta20(B2)Val --> Met] and Hb Saint Nazaire [beta103(G5)Phe --> Ile]. Other mechanisms leading to erythrocytosis are discussed, and finally, an algorithm is proposed for etiological diagnosis.
authors.affiliation: INSERM U654, Bases Moléculaire et Cellulaires des Malades Génétiques, Hôpital Henri Mondor, Créteil, France. Henri.Wajcman@im3.inserm.fr
authors.forename: Henri
authors.initials: H
authors.lastname: Wajcman
authors.forename: Frederic
authors.initials: F
authors.lastname: Galactéros
mesh_terms: D019794:2,3-Diphosphoglycerate / Q000737:chemistry / Q000378:metabolism; D014644:Genetic Variation / Q000235:genetics*; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D010100:Oxygen / Q000378:metabolism*; D011086:Polycythemia / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D006455:Hemoglobins, Abnormal; D019794:2,3-Diphosphoglycerate; D006418:Heme; D010100:Oxygen