Molecular defects of the coproporphyrinogen oxidase gene in hereditary coproporphyria.

S. Sassa, M. Kondo, S. Taketani, N. Nomura, K. Furuyama, R. Akagi, T. Nagai, M. Terajima, R. A. Galbraith, H. Fujita

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Hereditary coproporphyria (HCP) is an acute hepatic porphyria, and is an autosomal dominant disorder 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 approximately 50% of normal. Nucleotide sequence analysis of CPO cDNAs isolated from the proband's cells demonstrated 3 base substitutions which accompanied 3 different amino acid substitutions. An A514-->C transition causing an 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 were shown to be genetic polymorphisms. Transfection of CPO cDNA into E. 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. This mutation is different from three other mutations reported in patients with HCP. Molecular defects in the porphyrias including HCP are highly heterogeneous.

Original languageEnglish
Pages (from-to)59-66
Number of pages8
JournalCellular and molecular biology (Noisy-le-Grand, France)
Volume43
Issue number1
Publication statusPublished - 1997 Feb

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Molecular defects of the coproporphyrinogen oxidase gene in hereditary coproporphyria.'. Together they form a unique fingerprint.

Cite this