Unstable alpha‐chain hemoglobin variants with factitious beta‐thalassemia biosynthetic ratio: Hb questembert (α131[H14] Ser→Pro) and Hb Caen (α132[H15] Val→Gly)

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Abstract
Hb Questembert [α131(H14) Ser→Pro] was found in several members of a French family suffering from congenital Heinz body anemia. The unstable hemoglobin was expressed in the peripheral red blood cells at a very low level. Globin biosynthetic studies revealed a high specific activity of the abnormal chain and an α-/β-labeling ratio similar to that of β-thalassemia trait. Hb Caen [α132(H15) Val→Gly] is another unstable variant with the same globin biosynthesis abnormality. In both cases the structural modification is localized at the end of the H helix, a region encoded by the third exon. The mechanism for the unbalanced globin synthesis is not yet clear. It may be related 1) to a defect in chain assembly, 2) to an increased rate of degradation of the variant chain followed by the release of unlabeled β-chains from the abnormal hemoglobin, thus leading to an apparent suppression of β-chain synthesis, or 3) to a modified stability of the abnormal α-globin mRNA.