HB Watts [α74(EF3) OR α75(EF4)ASP→0]: A Shortened α Chain Variant Due to the Deletion of Three Nucleotides in Exon 2 of the α2-Globin Gene

Abstract

We have identified a new, slightly unstable α chain hemoglobin variant, present in a Mexican-American family. Amino acid sequencing and mass spectral analysis of the aberrant peptide (αT-9) of the variant revealed that the aspartic acid is deleted either at position 74 or 75 of one of the α-globin chains. Sequencing of the amplified α2- or α1-globin genes revealed a trinucleotide deletion (GAC) at codon 74 or 74 of the α2 gene. Although the aspartic acid residues of 74 and 75 of the α chain are neither a heme nor an inter chain contact, the slight instability of Hb Watts may be due to disturbance of the central cavity of hemoglobin by the deletion of an aspartic acid residue in the EF helix. Hb Watts is the first example of a trinucleotide deletion in the α2-globin gene.