title: Unstable and thalassemic alpha chain hemoglobin variants: a cause of Hb H disease and thalassemia intermedia.
abstract: We report an update of the alpha-globin gene point mutations resulting in structural modification associated with an alpha-thalassemia (alpha-thal) phenotype. These variants, barely symptomatic in the heterozygous state, are either unstable due to folding defects and/or defects in binding to alpha-hemoglobin stabilizing protein (AHSP). This is predicted to result in precipitation of the unstable alpha chains or Hb variant, a concomitant decrease in the overall quantity of normal alpha-globin in the red cells and a potential degree of anemia and possibly, hemolysis. Genotype/phenotype correlation and potential genetic risk in combination with common or less common alpha-thal defects are discussed.
authors.affiliation: INSERM U841, Créteil, France. henri.wajcman@inserm.fr
authors.forename: Henri
authors.initials: H
authors.lastname: Wajcman
authors.forename: Jan
authors.initials: J
authors.lastname: Traeger-Synodinos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papassotiriou
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudin-Creuza
authors.forename: John
authors.initials: J
authors.lastname: Old
mesh_terms: D011232:Chemical Precipitation; D014644:Genetic Variation; D005914:Globins / Q000737:chemistry / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D011485:Protein Binding; D017085:alpha-Thalassemia / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; D005914:Globins