Hb Nancy and Hb Osler: two distinct genetic variants with identical clinical and hemoglobin phenotype

Abstract Three hemoglobin variants (Hb Nancy, Osler and Fort Gordon), carrying the same Tyr→Asp substitution at position β145(HC2), have been independently described in 1975 in patients with marked polycythemia. The first one was found in a French Caucasian family from Lorraine, and the two others in African Americans. Two unrelated individuals with Hb Osler have been recently reinvestigated at the DNA level and surprisingly, in their β gene, codon 145 was found to be AAT which encodes for asparagine and not for aspartic acid, the aspartate at the protein level resulting, thus, from a very efficient posttranslational event. We reinvestigated a patient from the family of Hb Nancy and found that codon 145 was GAT, encoding for aspartate. This demonstrates that Hb Nancy is geneticaly distinct from Hb Osler despite an almost identical phenotype.