Hb Mississippi was discovered in a 6-year-old Chinese girl with chronic
anemia and
thalassemia intermedia. Family studies revealed that she had inherited the
Hb Mississippi from her father as well as inheriting a gene for
beta+-thalassemia from her mother. Electrophoretic analyses of the hemolysate of the father of the father and the proband on
polyacrylamide gels at pH 8.6 showed that the abnormal
hemoglobin had three distinct mobilities. A similar pattern was also observed by isoelectricfocusing. In addition, multiple abnormal peaks were observed by high performance liquid chromatographic
hemoglobin separations as well as high performance liquid chromatographic
globin chain separation. Structural analysis of the abnormal
hemoglobin demonstrated a single abnormality; the substitution of
serine to
cysteine at position 44 (CD3) of the
beta-globin chain. Since CD3 is on the surface of the
beta-globin chain, it was thought that polymerization of the abnormal
hemoglobin by
disulfide linkages might have been responsible for the anomalous behavior on electrophoresis and high performance liquid chromatography. Gel filtration chromatography on G-200
Sephadex confirmed this supposition and demonstrated that the abnormal
globin chain polymerized with itself as well as with other
globin chains.