title: Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria.
abstract: Variegate porphyria (VP) is an autosomal-dominant disorder that is caused by inheritance of a partial deficiency of the enzyme protoporphyrinogen oxidase (EC 1.3.3.4). It is characterized by cutaneous photosensitivity and/or various neurological manifestations. Protoporphyrinogen oxidase catalyses the penultimate step of haem biosynthesis, and mutations in the PPOX gene have been coupled to VP. In the present study, sequencing analysis revealed 10 different mutations in the PPOX gene in 14 out of 17 apparently unrelated Swedish VP families. Six of the identified mutations, 3G > A (exon 2), 454C > T (exon 5), 472G > C (exon 6), 614C > T (exon 6), 988G > C (exon 10) and IVS12 + 2T > G (intron 12), are single nucleotide substitutions, while 604delC (exon 6), 916-17delCT (exon 9) and 1330-31delCT (exon 13) are small deletions, and IVS12 + 2-3insT (intron 12) is a small insertion. Only one of these 10 mutations has been reported previously. Three of the mutations were each identified in two or more families, while the remaining mutations were specific for an individual family. In addition to the 10 mutations, one previously unreported single nucleotide polymorphism was identified. Mutation analysis of family members revealed two adults and four children who were silent carriers of the VP trait. Genetic analysis can now be added to the conventional biochemical analyses and used in investigation of putative carriers of a VP trait in these families.
authors.affiliation: Porphyria Centre Sweden, Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Wiman
authors.forename: P
authors.initials: P
authors.lastname: Harper
authors.forename: Y
authors.initials: Y
authors.lastname: Floderus
mesh_terms: D004252:DNA Mutational Analysis; D030541:Databases, Genetic; D004586:Electrophoresis; D005420:Flavoproteins; D005453:Fluorescence; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D024101:Mitochondrial Proteins; D009154:Mutation / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D017094:Porphyrias, Hepatic / Q000235:genetics*; D011166:Porphyrins / Q000032:analysis; D050768:Protoporphyrinogen Oxidase; D017422:Sequence Analysis, DNA; D013053:Spectrophotometry; D013548:Sweden
chemical_list: D005420:Flavoproteins; D024101:Mitochondrial Proteins; D011166:Porphyrins; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493978:PPOX protein, human; D050768:Protoporphyrinogen Oxidase