Hb J-CAPE TOWN [α92(FG4)Arg→Gln (α1), CGG→CAG] in Southern Italy Found in a Patient with Erythrocytosis

A high oxygen affinity hemoglobin (Hb) variant, Hb J-Cape Town [α92(FG4)Arg→Gln (α1), CGG→CAG] was identified in a 30-year-old woman patient from Cosenza (Southern Italy) who had previously been diagnosed with juvenile polycythemia in other hospitals. The occurrence of the variant Hb was assessed by both cation exchange chromatography and liquid chromatography-mass spectrometry (LC-MS) analyses. A detailed structural and functional characterization of the variant was performed at both the protein and DNA level. Structural investigation of the Hb variant by mass spectrometric methodologies and peptide sequencing identified the amino acid replacement as Arg→Gln at α92. The corresponding DNA mutation CGG→CAG was assigned to codon 92 of the α1 gene by DNA sequencing. These findings highlight the importance of investigating the hypothesis of a high affinity variant in the presence of a polycythemia so as to avoid unnecessary bone marrow examination or radioactive treatment. This report represents the first obs...