HB GOUDA [ALPHA-72(EF1)HIS-]GLN], A NEW SILENT ALPHA-CHAIN VARIANT

We describe a new alpha 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 no t detectable by starch gel electrophoresis but appears as a shoulder b efore the Hb A fraction during the chromatographic separation of Hb A( 1c). The hematological analysis revealed normal parameters with a norm al serum iron value. No anomalies were reported in connection with Hb Gouda. The tryptic peptide map and sequencing of the alpha T-9 peptide revealed the substitution of a histidine by a glutamine at position 7 2. By selective amplification and sequencing of both the alpha genes, we have assigned the new mutation to the alpha 2 gene. Position 72 of the alpha chain is a moderately conserved site located between two non -conserved amino acids. This site is not involved in heme, dimer or te tramer contacts, or in Bohr effect or in 2,3-diphosphoglycerate bindin g.