title: A molecular defect in human protoporphyria.
abstract: Protoporphyria is generally an autosomal dominant disease that is characterized clinically by photosensitivity and hepatobiliary disease and that is characterized biochemically by elevated protoporphyrin levels. The enzymatic activity of ferrochelatase, which catalyzes the last step in the heme biosynthetic pathway, is deficient in all tissues of patients with protoporphyria. In this study, sequencing of ferrochelatase cDNAs from a patient with protoporphyria revealed a single point mutation in the cDNAs resulting in the conversion of a Phe(TTC) to a Ser(TCC) in the carboxy-terminal end of the protein, F417S. Further, the human ferrochelatase gene was mapped to chromosome 18q21.3 by chromosomal in situ suppression hybridization. Finally, expression of recombinant ferrochelatase in Escherichia coli demonstrated a marked deficiency in activity of the mutant ferrochelatase protein and of mouse-human mutant ferrochelatase chimeric proteins. Therefore, a point mutation in the coding region of the ferrochelatase gene is the genetic defect in some patients with protoporphyria.
authors.affiliation: Department of Medicine, UCSD, La Jolla 92093-0623.
authors.forename: D A
authors.initials: DA
authors.lastname: Brenner
authors.forename: J M
authors.initials: JM
authors.lastname: Didier
authors.forename: F
authors.initials: F
authors.lastname: Frasier
authors.forename: S R
authors.initials: SR
authors.lastname: Christensen
authors.forename: G A
authors.initials: GA
authors.lastname: Evans
authors.forename: H A
authors.initials: HA
authors.lastname: Dailey
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D004247:DNA / Q000235:genetics; D005294:Ferrochelatase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D011164:Porphyrias / Q000235:genetics*; D011524:Protoporphyrins / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000302:isolation & purification
chemical_list: D009838:Oligodeoxyribonucleotides; D011524:Protoporphyrins; D012313:RNA; D004247:DNA; D005294:Ferrochelatase