title: Frameshift mutations in exons 9 and 10 of the porphobilinogen deaminase gene produce a crossreacting immunological material (CRIM)-negative form of acute intermittent porphyria.
abstract: Single-strand conformation polymorphism analysis was used to screen all 15 exons of the porphobilinogen deaminase gene from 13 patients with acute intermittent porphyria. Unique banding patterns in two amplified gene fragments, one containing exon 9 and another containing exon 10, were further investigated. Sequence analysis of cloned genomic DNA revealed a single base pair insertion in the middle of exon 9 in one patient and a single base pair deletion near the 3' end of exon 10 in two related patients. Both mutations change the reading frame of the mRNA transcript and predict proteins that are normal at their NH2-terminal ends but contain novel, unrelated sequences at their COOH-terminal ends and are prematurely terminated. Frameshift mutations in the porphobilinogen deaminase gene are uncommon; this is the first report of an insertion mutation causing acute intermittent porphyria.
authors.affiliation: Division of Clinical Chemistry, Vancouver General Hospital, British Columbia, Canada.
authors.forename: W E
authors.initials: WE
authors.lastname: Schreiber
authors.forename: F
authors.initials: F
authors.lastname: Fong
authors.forename: A
authors.initials: A
authors.lastname: Jamani
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons / Q000235:genetics*; D016368:Frameshift Mutation; D017353:Gene Deletion; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D017118:Porphyria, Acute Intermittent / Q000201:enzymology* / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004247:DNA; D011163:Hydroxymethylbilane Synthase