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

Blood Cells Mol Dis. Nov-Dec 2009;43(3):235-8. doi: 10.1016/j.bcmd.2009.08.006. Epub 2009 Sep 15.

Abstract

A new unstable beta globin chain variant associated with methemoglobin (Met-Hb) phenotype was found in a Caucasian infant. Molecular analysis of the beta 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 [GGT/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 beta 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.

Publication types

  • Case Reports

MeSH terms

  • Exons / genetics
  • Genetic Variation
  • Genotype
  • Humans
  • Infant
  • Male
  • Methemoglobin / chemistry
  • Methemoglobin / genetics*
  • Mutation / genetics
  • Phenotype
  • Sequence Deletion*
  • beta-Globins / genetics*

Substances

  • beta-Globins
  • Methemoglobin