Unstable and thalassemic alpha chain hemoglobin variants: a cause of Hb H disease and thalassemia intermedia.
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.
Wajcman
Henri
H
INSERM U841, Créteil, France. henri.wajcman@inserm.fr
Traeger-Synodinos
Jan
J
Papassotiriou
Ioannis
I
Giordano
Piero C
PC
Harteveld
Cornelis L
CL
Baudin-Creuza
Véronique
V
Old
John
J
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*
D006455:Hemoglobins, Abnormal; D005914:Globins