The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria

Journal Article · Wed Jan 01 04:00:00 EST 1992 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.89.1.281· OSTI ID:5489630

Nakahashi, Yoshitsugu; Taketani, Shigeru ^[1]; Fujita, Hiroyoshi; Ishida, Nobuhiro; Kappas, Attallah; Sassa, Shigeru ^[2]

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1. Kansai Medical Univ., Moriguchi (Japan)
2. Rockefeller Univ. Hospital, New York, NY (United States)

The molecular basis of an inherited defect of ferrochelatase in a patient with erythropoietic protoporphyria (EPP) was investigated. Ferrochelatase is the terminal enzyme in the heme biosynthetic pathway and catalyzes the insertion of ferrous iron into protoporphyrin IX to form heme. In Epstein-Barr virus-transformed lymphoblastoid cells from a proband with EPP, enzyme activity, an immunochemically quantifiable protein, and mRNA content of ferrochelatase were about one-half the normal level. In contrast, the rate of transcription of ferrochelatase mRNA in the proband's cells was normal, suggesting that decreased ferrochelatase mRNA is due to an unstable transcript. cDNA clones encoding ferrochelatase in the proband, isolated by amplification using the polymerase chain reaction, were found to be classified either into those encoding the normal protein or into those encoding an abnormal protein that lacked exon 2 of the ferrochelatase gene, indicating that the proband is heterozygous for the ferrochelatase defect. Genomic DNA analysis revealed that the abnormal allele had a point mutation, C {yields} T, near the acceptor site of intron 1. This point mutation appears to be responsible for the post-transcriptional splicing abnormality resulting in an aberrant transcript of ferrochelatase in this patient.

• OSTI ID: 5489630
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 89:1; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL PATHWAYS
BLOOD FORMATION
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
ENZYME ACTIVITY
ERYTHROPOIESIS
GENE AMPLIFICATION
GENE MUTATIONS
HEME
HEREDITARY DISEASES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MOLECULAR BIOLOGY
MUTATIONS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATIENTS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PIGMENTS
PORPHYRINS
RADIOISOTOPES
RECOMBINANT DNA
TRANSCRIPTION