A novel mutation of the cytochrome-b5 reductase gene in an Indian patient: the molecular basis of type I methemoglobinemia

Haematologica. 2006 Nov;91(11):1542-5.

Abstract

We report here a novel mutation in the cytochrome b5 reductase gene resulting in type I methemoglobinemia. A single T->C transition in exon 8 at position 25985 was identified, changing codon 217 from Leu to Pro (L217P). The mutation is located in the NADH binding domain at the base of alpha-helix Nalpha3, a region of sequence highly conserved from yeast to man. A quantitative assessment of the thermodynamic cost of this mutation at 37 degrees C revealed a ten-fold drop in the free energy of stability. Alterations in hydrogen bonding and solvent accessibility surrounding residue 217 were predicted based on computer modeling.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cytochrome-B(5) Reductase / chemistry
  • Cytochrome-B(5) Reductase / genetics*
  • Female
  • Genotype
  • Humans
  • India
  • Male
  • Methemoglobinemia / enzymology*
  • Methemoglobinemia / genetics*
  • Mutation*
  • Thermodynamics

Substances

  • Cytochrome-B(5) Reductase