An elongated C-terminal hemoglobin variant, due to the deletion of nucleotide A in codon 144 (nucleotide 63600 GenBank entry UO1317) was found in a 31-year-old woman from Trento (northeastern Italy). This deletion led to the replacement of lysine at beta144 by a serine residue, the disappearance of the stop codon at position 147, and the presence of 12 additional residues, identical to those observed in Hbs Saveme, Tak and Cranston, which result from a similar mechanism. Hb Trento, amounting to 29% of the total hemoglobin, was unstable and had, as the other variants of this group, an increased oxygen affinity. It led to a mild compensated hemolytic anemia with red cell inclusion bodies. Functional studies of the isolated abnormal hemoglobin were difficult to perform because of autoxidation, precipitation, and formation of hybrids with Hb A.

(1999). Hb Bologna-St. Orsola [β146(HC3)His→Tyr]: a New High Oxygen Affinity Variant with Halved Bohr Effect and Highly Reduced Reactivity Towards 2,3-Diphosphoglycerate. Hemoglobin: Vol. 23, No. 4, pp. 353-359.

Hb Gàmbara is a new hemoglobin variant with abnormal beta chains that has been found in three out of four members of a family of Lombardy origin (Gàmbara, Brescia, Northern Italy). The affected subjects led a normal life, but they had modest erythrocytosis and mild (compensated) hemolysis with slight splenomegaly. Their abnormal hemoglobin was about 52% of the total hemoglobin, and was shown to be stable by the isopropanol test. Whole blood P50 of the proband was 19.3 Torr, Bohr effect was decreased (-0.25), as well as the molar ratio between the 2,3-diphosphoglycerate level and total hemoglobin of erythrocytes (0.68). The purified abnormal hemoglobin was characterized by an altered oxygen affinity, low n-factor, chloride, and 2,3-diphosphoglycerate effects. The Bohr effect was about 40% of the normal control. The abnormal hemoglobin moved faster than Hb A at alkaline electrophoresis, and split into two fractions, probably due to the formation of hybrid tetramers (alpha 2 beta A beta X). The reversed phase high performance liquid chromatogram from the tryptic digest of the aminoethylated abnormal beta chain subunits indicated the presence of an extra peptide, beta T-9, 10, replacing the individual peptides beta T-9 and beta T-10. Finally, the proband's DNA, drawn from a suitable segment of the beta structural gene (exon 2), revealed a nucleotide sequence carrying the heterozygous mutation AAG-->GAG at codon 82. This led to a Lys-->Glu substitution at position 82(EF6) of the beta chain.