Molecular Interactions Between Hb 
-G Philadelphia, HbC, and HbS: Phenotypic Implications for SC -G Philadelphia Disease
Christine Lawrence,
Rhoda Elison Hirsch,
Nazim A. Fataliev,
Snehal Patel,
Mary E. Fabry, and
Ronald L. Nagel
From the Division of Hematology, Albert Einstein College of Medicine/Montefiore Medical Center and Jacobi Medical Center, Bronx, NY.
We show here that 
G-Phila.2
C2 has an increased rate of crystal nucleation compared to 2 C2 (HbC). We conclude from this finding that position 68, the mutation site of G-Phila.2 2 (HbGPhiladelphia), is a contact site in the crystal of HbC. In addition, that HbS enhances HbC crystallization (additive to the effect of G-Phila, as shown here) and that G-Phila. inhibits polymerization of HbS are pathogenically relevant previously known facts. All of these findings help explain the phenotype of an individual simultaneously heterozygous for the S, C, and the G-Phila. genes (SC-G Philadelphia disease). This disease is characterized by a mild clinical course, abundant circulating intraerythrocytic crystals, and increased folded red cells. This phenotype seems to be the result of increased crystallization and decreased polymerization brought about by the opposite effects of the gene product of the G-Phila. gene on the C and S gene products. Some of the intraerythrocytic crystals in this syndrome are unusually long and thin, resembling sugar canes, unlike those seen in SC disease. The mild clinical course associated with increased crystallization implies that, in SC disease, polymerization of HbS is pathogenically more important than the crystallization induced by C chains. The SC-G Philadelphia disease is an example of multiple hemoglobin chain interactions (epistatic effect among globin genes) creating a unique phenotype.
Blood, Vol. 90 No. 7 (October 1), 1997:
pp. 2819-2825
© 1997 by The American Society of Hematology.
