title: 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.
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.
authors.affiliation: Research Laboratory for Genetic Information, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Katsube
authors.forename: N
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: R
authors.initials: R
authors.lastname: Seki
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: K
authors.initials: K
authors.lastname: Tanishima
authors.forename: A
authors.initials: A
authors.lastname: Tomoda
authors.forename: E
authors.initials: E
authors.lastname: Takazakura
authors.forename: T
authors.initials: T
authors.lastname: Yubisui
authors.forename: M
authors.initials: M
authors.lastname: Takeshita
mesh_terms: D000328:Adult; D001483:Base Sequence; D002874:Chromosome Mapping; D003579:Cytochrome Reductases / Q000172:deficiency* / Q000235:genetics; D042966:Cytochrome-B(5) Reductase; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific; D005091:Exons; D006720:Homozygote; D006801:Humans; D007438:Introns; D008297:Male; D008708:Methemoglobinemia / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011487:Protein Conformation
chemical_list: D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific