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. 1991 Apr;48(4):799–808.

Exonic point mutations in NADH-cytochrome B5 reductase genes of homozygotes for hereditary methemoglobinemia, types I and III: Putative mechanisms of tissue-dependent enzyme deficiency

Takanori Katsube, Norihiro Sakamoto, Yasushi Kobayashi, Ritsuko Seki, Masami Hirano, Kiyoh Tanishima, Akio Tomoda, Eisuke Takazakura, Toshitsugu Yubisui, Masazumi Takeshita, Yoshiyuki Sakaki, Yasuyuki Fukumaki
PMCID: PMC1682939  PMID: 1707593

Abstract

We analyzed the NADH-cytochrome b5 reductase gene of hereditary methemoglobinemia type I and type III, by using PCR-related techniques. The mutation in type I is a guanine-to-adenine substitution in codon 57 of exon 3 of the NADH-cytochrome b5 reductase gene, and the sense of this codon is changed from arginine to glutamine. In type III the mutation is a thymine-to-cytosine transition in codon 148 of exon 5, causing leucine-to-proline replacement in type III. The former mutation abolishes the MspI recognition site. Homozygosity for the former mutation in a patient with type I was confirmed by restriction analysis of PCR-amplified fragments and by dot blot hybridization of amplified products with allele-specific oligonucleotide probes. The latter mutation generates a recognition site for MspI. Amplification of exon 5 by PCR followed by digestion with MspI revealed homozygosity for this mutation in patients with type III. Putative mechanisms of tissue-dependent enzyme defects in hereditary methemoglobinemia are discussed.

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