title: Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria.
abstract: Variegate porphyria (VP) is an acute hepatic porphyria with autosomal dominant inheritance due to a partial deficiency of protoporphyrinogen oxidase (PPOX) activity. The molecular defect responsible for VP was investigated by sequencing PPOX gene coding sequence from four patients in three unrelated VP families of French Caucasian origin. In a first patient, a point insertion of a G at position 1022 of the cDNA, produced a frameshift resulting in a premature stop codon. In three other patients from two unrelated families we found a missense point mutation leading to glycine to arginine substitution (G232R) in exon 7. This Gly232 appears to be a strictly conserved residue through evolution. In one VP family, we observed the cosegregation of the G232R missense mutation and the deficient PPOX activity. The mutations reported here are the first to be described in patients with VP and support the conclusion that PPOX gene defects are disease causing mutations in human variegate porphyria.
authors.affiliation: Centre Français des Porphyries, INSERM U409, Hôpital Louis Mourier, Colombes, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Deybach
authors.forename: H
authors.initials: H
authors.lastname: Puy
authors.forename: A M
authors.initials: AM
authors.lastname: Robréau
authors.forename: J
authors.initials: J
authors.lastname: Lamoril
authors.forename: V
authors.initials: V
authors.lastname: Da Silva
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Y
authors.initials: Y
authors.lastname: Nordmann
mesh_terms: D000595:Amino Acid Sequence; D005260:Female; D005420:Flavoproteins; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010375:Pedigree; D011110:Polymorphism, Genetic; D017094:Porphyrias, Hepatic / Q000235:genetics*; D050768:Protoporphyrinogen Oxidase
chemical_list: D005420:Flavoproteins; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493978:PPOX protein, human; D050768:Protoporphyrinogen Oxidase