A New α-Globin Variant with Increased Oxygen Affinity in a Swiss Family: Hb Frauenfeld [α138(H21)Ser→Phe, TCC>TTC (α 2)]

Abstract

A new α-globin mutation [α138(H21)Ser→Phe] was found in a 55-year-old male proband with an erythrocytosis known since his youth. Cation exchange high performance liquid chromatography (HPLC) revealed an additional peak eluting slightly before Hb A indicating the presence of a variant. The peak area of the variant was approximately one-third that of Hb A suggesting an α-globin variant. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis confirmed the mutation at the protein level. The variant is also detectable with isoelectric focusing and reversed phase HPLC. DNA analysis revealed a heterozygous sequence mutation at codon 138 of the α2 gene. A C>T transition at the second nucleotide of the codon indicated a Ser→Phe exchange. The variant showed increased oxygen affinity and was named Hb Frauenfeld.

Keywords:

• α-Globin variant
• PolyCAT A
• High performance liquid chromatography (HPLC)
• Mass spectrometry (MS)
• Erythrocytosis

Notes

*The first two authors contributed equally to this study.