HB-WATTS [ALPHA-74(EF3) OR ALPHA-75(EF4)ASP-]0] - A SHORTENED ALPHA-CHAIN VARIANT DUE TO THE DELETION OF 3 NUCLEOTIDES IN EXON-2 OF THE ALPHA-2-GLOBIN GENE

We have identified a new, slightly unstable ex chain hemoglobin varian t, present in a Mexican-American family. Amino acid sequencing and mas s spectral analysis of the aberrant peptide (alpha T-9) of the variant revealed that the aspartic acid is deleted either at position 74 or 7 5 of one of the alpha-globin chains. Sequencing of the amplified alpha 2- or alpha 1-globin genes revealed a trinucleotide deletion (GAG) at codon 74 or 74 of the alpha 2 gene. Although the aspartic acid residu es of 74 and 75 of the alpha chain are neither a heme nor an inter cha in contact, the slight instability of Hb Watts may be due to disturban ce 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 trinu cleotide deletion in the alpha 2-globin gene.