Hb M Dothan [β 25/26 (B7/B8)/(GGT/GAG→GAG//Gly/Glu→Glu]; a new mechanism of unstable methemoglobin variant and molecular characteristics

Abstract

A new unstable β globin chain variant associated with methemoglobin (Met-Hb) phenotype was found in a Caucasian infant. Molecular analysis of the β globin gene using polymerase chain reaction (PCR) amplification and sequencing led to the detection of a new in frame deletion in exon-1. Direct sequencing of the PCR product revealed a 3 bp deletion (−GTG) between codons 25/26, which resulted in the loss of a single amino acid (−Gly). We propose that this newly discovered unstable M-hemoglobin (M-Hb) variant, named Hb Dothan [G GT/GAG→GAG//Gly/Glu→Glu], is caused by a shift in the amino acid sequence and altered packing of the B and E helices during β globin synthesis, and also changes the orientation of the critical proximal and distal histidine in the F and E helices respectively. Phenotype/Genotype features and molecular characteristics of this new beta chain are presented in this communication.