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

Roberto H Nussenzveig, H Bindu Lingam, Amos Gaikwad, Qiqing Zhu, Naijie Jing, Josef T Prchal

Department of Medicine, Baylor College of Medicine, Houston, Texas, 77030, USA.

Haematologica 2006 Nov

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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.

Citation

Roberto H Nussenzveig, H Bindu Lingam, Amos Gaikwad, Qiqing Zhu, Naijie Jing, Josef T Prchal. 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