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

研究成果: Article査読

29 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1807-1810
ページ数4
ジャーナルHuman molecular genetics
3
10
DOI
出版ステータスPublished - 1994 10月
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 遺伝学
  • 遺伝学(臨床)

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