Hemoglobin S Antilles: a variant with lower solubility than hemoglobin S and producing sickle cell disease in heterozygotes.
We have found a sickling variant, Hb S Antilles, alpha 2 beta 2(6 Glu----Val, 23 Val----Ile), that has the same electrophoretic mobility as Hb S but a distinct isoelectric focus and produces sickling in the carriers of the Hb A/S Antilles trait. The carriers' erythrocytes tend to sickle at O2 partial pressures similar to those that induce sickling in Hb S/C disease. Pure deoxy-Hb S Antilles is 50% as soluble as deoxy-Hb S (saturating concentration = 11 g X dl-1 compared to 18.4 for Hb S). Dilute solutions of pure Hb S Antilles have a lower oxygen affinity than those of Hb A or Hb S (partial pressure for 50% binding is 9 mm Hg compared to 5.5 mm Hg for Hb A or S at pH 7.00). A/S Antilles erythrocytes have a much lower oxygen affinity than A/S cells; this is further decreased in dense cells fractionated on a Percoll density gradient. Their oxygen equilibrium curves had anomalous shapes like those of S/S cells. Fiber formation in the erythrocytes of Hb S Antilles carriers is clearly due to its low solubility and oxygen affinity, showing that heterozygosity for this hemoglobin presents another sickle cell syndrome and suggesting that Hb S heterozygotes who exhibit symptoms of sickle cell disease should be carefully screened for double mutations.
Monplaisir
N
N
Merault
G
G
Poyart
C
C
Rhoda
M D
MD
Craescu
C
C
Vidaud
M
M
Galacteros
F
F
Blouquit
Y
Y
Rosa
J
J
D000595:Amino Acid Sequence; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics*; D004913:Erythrocytes, Abnormal / Q000473:pathology; D005782:Gels; D005914:Globins / Q000235:genetics; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007526:Isoelectric Point; D009154:Mutation; D010108:Oxyhemoglobins / Q000378:metabolism; D012995:Solubility
D005782:Gels; D006451:Hemoglobin, Sickle; D010108:Oxyhemoglobins; C055657:hemoglobin S-Antilles; D005914:Globins