Characterization and expression of cDNA encoding coproporphyrinogen oxidase from a patient with hereditary coproporphyria

Hiroyoshi Fujita, Masao Kondo, Shigeru Taketani, Nakao Nomura, Kazumichi Furuyama, Relko Akagi, Tadashi Nagai, Masanori Terajima, Richard A. Galbraith, Shigeru Sassa

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Hereditary coproporphyria (HCP) is an acute hepatic porphyria with autosomal dominant inheritance, but with a variable degree of clinical expression. Molecular cloning, sequencing and expression of the defective gene for coproporphyrinogen oxidase (CPO) in a patient with HCP were carried out. Enzyme assays revealed that CPO activity in EBV-transformed lymphoblastoid cells from the proband and one of her sisters was ≈ 50% of normal. Nucleotide sequence analysis of CPO cDNAs isolated from the proband's cells demonstrated three base substitutions, and three accompanying amino acid substitutions. An A514 → C transition causing a Asn172 → His substitution occurred in one allele, while two other transitions, G265 → A and G580 → A, caused Gly89 → Ser and Val194 → Ile substitutions, respectively, in the other allele. The A514 → C and the G580 → A transitions are known genetic polymorphisms. Transfection of CPO cDNA into Escherichia coli demonstrated that cDNA with the G265 → A transition produced a protein with less than 5% of normal enzyme activity. These findings indicate that the G265 → A transition, involving the highly conserved glycine residue at the 89th position, is responsible for the CPO defect in the patient and accounts for the partial deficiency of CPO activity in this pedigree.

Original languageEnglish
Pages (from-to)1807-1810
Number of pages4
JournalHuman molecular genetics
Volume3
Issue number10
DOIs
Publication statusPublished - 1994 Oct

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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