HB SAINT NAZAIRE (BETA-103G5!PHE-!LLE) - A NEW EXAMPLE OF POLYCYTHEMIA DUE TO A HEMOGLOBIN-VARIANT WITH INCREASED OXYGEN-AFFINITY

Hb Saint Nazaire beta103 (G5) Phe-->Ile! was found in four apparently unrelated French families. The five patients carrying this hemoglobin have been detected because of a moderate erythrocytosis. The structur al abnormality of Hb Saint Nazaire concerns the same residue as in Hb Heathrow beta103 (G5) Phe-->Leu). A comparative functional study betw een these two variants showed that the increase in oxygen affinity is much lower in Hb Saint Nazaire than in Hb Heathrow. The replacement of phenylalanine G5, which is localized within the heme pocket, by a leu cine abolishes several contacts between the heme and the globin and le ads to an environment of the heme having some similarities with that o bserved in myoglobin. In contrast, the replacement of G5 by an isoleuc ine is likely to introduce less structural modifications. (C) 1993 Wil ey-Liss, Inc.