HbC compound heterozygotes [HbC/Hb Riyadh and HbC/Hb N-Baltimore] with opposing effects upon HbC crystallization.
Compound heterozygotes of variant haemoglobins (Hbs) with HbC, with or without novel phenotypic changes, have provided insight into the molecular basis of the interacting haemoglobins and information concerning the role of specific residues in the crystallization of oxy HbC. A high phosphate buffer system has proved useful for studying the effects of variant haemoglobins (naturally co-existing with HbC in the red cell) on the oxy HbC crystallization process and has led us to conclude that beta87 and beta73 are contact sites of the oxy HbC crystal. We now present investigations from two HbC compound heterozygotes which exhibit opposing effects upon HbC crystallization: HbC/Hb N-Baltimore (beta95 Lys-->Glu) and HbC/Hb Riyadh (beta120 Lys-->Asn). The latter inhibits the in vitro crystallization of HbC, explaining the lack of erythrocyte abnormalities (with the exception of microcytosis) in the doubly heterozygous infant. In contrast, Hb N-Baltimore accelerates the crystallization of HbC, contributing to multiple abnormalities in red cell morphology, albeit in the absence of morbidity. We conclude that (1) beta120 and beta95 are additional contact sites in the crystal, and (2) the HbC/Hb Riyadh haemoglobinopathy demonstrates that crystallization may not be required for the generation of the observed microcytosis and increased red cell density in HbC-containing red cells.
Hirsch
R E
RE
Department of Medicine, The Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Witkowska
H E
HE
Shafer
F
F
Lin
M J
MJ
Balazs
T C
TC
Bookchin
R M
RM
Nagel
R L
RL
D000328:Adult; D003460:Crystallization; D004586:Electrophoresis; D006444:Hemoglobin C / Q000235:genetics*; D006445:Hemoglobin C Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007525:Isoelectric Focusing; D009994:Osmolar Concentration
D006444:Hemoglobin C