title: Identification of the first variegate porphyria mutation in an indigenous black South African and further evidence for heterogeneity in variegate porphyria.
abstract: Variegate porphyria is an autosomal dominant disorder of haem metabolism resulting from reduced levels of the penultimate enzyme in the pathway, protoporphyrinogen oxidase. Here we investigate the molecular basis of variegate porphyria in four non-R59W South African families. We report the identification of the first mutation in the protoporphyrinogen oxidase gene in a black South African individual (V290M). In addition, we document three further mutations, a missense mutation (L15F), a deletion followed by a substitution [c769delG;770T > A], and a nonsense mutation (Q375X), in individuals of European or mixed ancestry. Our data provide further evidence of genetic heterogeneity in South Africa.
authors.affiliation: Lennox Eales Porphyria Laboratories, University of Cape Town Medical School, Observatory Cape Town 7925, 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: L M
authors.initials: LM
authors.lastname: Davids
authors.forename: V
authors.initials: V
authors.lastname: Hancock
authors.forename: D
authors.initials: D
authors.lastname: Meissner
authors.forename: R E
authors.initials: RE
authors.lastname: Kirsch
authors.forename: P N
authors.initials: PN
authors.lastname: Meissner
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D018389:Codon, Nonsense; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005420:Flavoproteins; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010088:Oxidoreductases / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D018807:Polymorphism, Single-Stranded Conformational; D017094:Porphyrias, Hepatic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D050768:Protoporphyrinogen Oxidase; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D013019:South Africa
chemical_list: D018389:Codon, Nonsense; D005420:Flavoproteins; D024101:Mitochondrial Proteins; D004247:DNA; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493978:PPOX protein, human; D050768:Protoporphyrinogen Oxidase