Hb Gouda [α72(EF1)HIS→GLN], a new Silent α Chain Variant

Abstract

We describe a new a chain mutant accidentally found in a diabetic patient. The propositus is being treated for diabetes mellitus II with 4% glycated hemoglobin (Hb A_1c). The variant, named Hb Gouda, is not detectable by starch gel electrophoresis but appears as a shoulder before the Hb A fraction during the chromatographic separation of Hb A_1c. The hematological analysis revealed normal parameters with a normal serum iron value. No anomalies were reported in connection with Hb Gouda. The tryptic peptide map and sequencing of the αT-9 peptide revealed the substitution of a histidine by a glutamine at position 72. By selective amplification and sequencing of both the α genes, we have assigned the new mutation to the α2 gene. Position 72 of the α chain is a moderately conserved site located between two non-conserved amino acids. This site is not involved in heme, dimer or tetramer contacts, or in Bohr effect or in 2,3-diphosphoglycerate binding.