Hb Kochi [β141(H19)Leu→Val (g.1404 C→G); 144–146(HC1-3)Lys-Tyr-His→0 (g.1413 A→T)]: A New Variant with Increased Oxygen Affinity

Abstract

A novel hemoglobin (Hb) variant was found in a specimen that showed an unusual profile in analyses of glycohemoglobin. An abnormal β-globin, 443 Da smaller than normal β-globin, was detected by electrospray ionization mass spectrometry (ESI/MS) with intact globin. Mass spectrometry analysis of tryptic peptides derived from isolated abnormal Hb showed an abnormal peptide, characterized as βT-14 (141Leu→Val and 144Lys→0). Nucleotide sequencing revealed a heterozygosity of codon 141 C TG(Leu)→G TG(Val), and codon 144 A AG(Lys)→T AG(stop codon). The isopropanol stability test was normal. We named this novel variant Hb Kochi for the district where it was found. Functional studies carried out on diluted whole hemolysates and isolated Hb components from the proband demonstrated an increased oxygen affinity, consistent with the existence of mild erythrocytosis.

• Hb Kochi
• Electrospray ionization mass spectrometry (ESI/MS)
• Two-point mutations on one β-globin gene
• High oxygen affinity