DNA Sequence Analysis Proves HB M-Milwaukee-2 is DUE to β-Globin Gene Codon 92 (CAC→TAC), The Presumed Mutation of HB M-Hyde Park HB M-Akita

Abstract

Among the causes of congenital methemoglobinemia, Hb M-Milwaukee-2 was one of the earliest described, in a patient who also had Hb E trait. The structure of Hb M-Milwaukee-2 has been elusive. DNA sequence analysis, as here reported, proves that this hemoglobin variant is due to the mutation CACTAC at codon 92 of the β-globin gene, corresponding to the substitution of tyrosine for histidine. This mutation is identical with that presumed to be the cause of Hb M-Hyde Park Hb M-Akita. In addition, the DNA mutation of Hb E, GAGAAG at codon 26, was confirmed in this case.