title: Homozygous variegate porphyria in South Africa: genotypic analysis in two cases.
abstract: Variegate porphyria is an autosomal dominant disorder of heme metabolism which results from decreased activity of the enzyme protoporphyrinogen oxidase. Clinically, the disease manifests postpubertally and is characterized by photocutaneous sensitivity and/or acute neurovisceral crises. However, in homozygous variegate porphyria, onset of the disease usually occurs in infancy with severe skin manifestations. The molecular basis of variegate porphyria in two severely affected probands in two South African families is described. Mutation detection included combined SSCP-heteroduplex analysis followed by direct sequencing. The unrelated probands both had the common R59W mutation while the other lesion was Y348C or R138P (both novel mutations), causing homozygous variegate porphyria.
authors.affiliation: Department of Medicine, University of Cape Town Medical School, South Africa.
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; D019943:Amino Acid Substitution; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005420:Flavoproteins; D005838:Genotype; D020180:Heteroduplex Analysis; D006720:Homozygote; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D017094:Porphyrias, Hepatic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D050768:Protoporphyrinogen Oxidase; D013019:South Africa
chemical_list: D005420:Flavoproteins; D024101:Mitochondrial Proteins; D004247:DNA; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493978:PPOX protein, human; D050768:Protoporphyrinogen Oxidase