Unstable alpha-chain hemoglobin variants with factitious beta-thalassemia biosynthetic ratio: Hb Questembert (alpha 131[H14]Ser-->Pro) and Hb Caen (alpha 132[H15]Val-->Gly).
Hb Questembert [alpha 131(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 alpha-/beta-labeling ratio similar to that of beta-thalassemia trait. Hb Caen [alpha 132(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 beta-chains from the abnormal hemoglobin, thus leading to an apparent suppression of beta-chain synthesis, or 3) to a modified stability of the abnormal alpha-globin mRNA.
Wajcman
H
H
INSERM U299, CHU de Bicêtre, France.
Vasseur
C
C
Blouquit
Y
Y
Rosa
J
J
Labie
D
D
Najman
A
A
Reman
O
O
Leporrier
M
M
Galacteros
F
F
D000328:Adult; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004586:Electrophoresis; D005260:Female; D006454:Hemoglobins / Q000096:biosynthesis / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D007525:Isoelectric Focusing; D010449:Peptide Mapping; D017086:beta-Thalassemia / Q000097:blood / Q000378:metabolism*
D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; C081236:hemoglobin Caen; C081235:hemoglobin Questembert