title: Identification and characterisation of a deletion (537delAT) in the protoporphyrinogen oxidase gene in a South African variegate porphyria family.
abstract: Variegate porphyria is an autosomal dominant disorder of haem metabolism resulting from a partial decrease in protoporphyrinogen oxidase activity. Variegate porphyria is highly prevalent in South Africa, the result of a founder effect now confirmed genetically as a single point mutation (R59W) which has been described in nearly all South African variegate porphyria patients studied. Only two other mutations (H20P, R168C) have been reported in South Africa. We utilised simultaneous, single-stranded conformational polymorphism and heteroduplex analysis, and direct sequencing to identify a further mutation; a 2 bp deletion in exon 6 which results in a premature stop codon 11 codons downstream from the mutation and is the first reported deletion in the protoporphyrinogen oxidase gene in a South African family. The familial segregation of this mutation strongly suggests that it is the disease causing mutation for variegate porphyria in this family. This further evidence for allelic heterogeneity limits the utility of tests for the R59W mutation in the diagnosis of variegate porphyria in South Africa.
authors.affiliation: MRC/UCT Liver Research Centre, Department of Medicine, University of Cape Town Medical School, Observatory, South Africa. anne@liver.uct.ac.za
authors.forename: A V
authors.initials: AV
authors.lastname: Corrigall
authors.forename: R J
authors.initials: RJ
authors.lastname: Hift
authors.forename: V
authors.initials: V
authors.lastname: Hancock
authors.forename: D
authors.initials: D
authors.lastname: Meissner
authors.forename: L
authors.initials: L
authors.lastname: Davids
authors.forename: R E
authors.initials: RE
authors.lastname: Kirsch
authors.forename: P N
authors.initials: PN
authors.lastname: Meissner
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D004247:DNA / Q000097:blood; D005260:Female; D005420:Flavoproteins; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009692:Nucleic Acid Heteroduplexes / Q000032:analysis*; D010088:Oxidoreductases / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D017094:Porphyrias, Hepatic / Q000235:genetics*; D050768:Protoporphyrinogen Oxidase; D017384:Sequence Deletion / Q000235:genetics*; D013019:South Africa
chemical_list: D005420:Flavoproteins; D024101:Mitochondrial Proteins; D009692:Nucleic Acid Heteroduplexes; D004247:DNA; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493978:PPOX protein, human; D050768:Protoporphyrinogen Oxidase