title: Acute intermittent porphyria: the in vitro expression of mutant hydroxymethylbilane synthase.
abstract: Acute intermittent porphyria (AIP) is an inborn error of haem biosynthesis caused by a variety of mutations in the gene coding for hydroxymethylbilane synthase (HMB-S). The entire coding sequence of this gene, from each of three South African AIP patients, was therefore screened for mutations using chemical cleavage mismatch (CCM) analysis and any changes detected characterized by DNA sequencing. Three single base changes were identified; a G77 to A in exon 3, a C346 to T in exon 8 and a G518 to A in exon 10. These missense mutations, previously reported to be present in other populations, are known to be responsible for the structurally deleterious amino acid replacements R26H, R116W and R173Q, respectively. The in vitro expression of the enzymes containing these mutations and the subsequent measurement of their specific activities revealed a reduction to approximately 4% of normal activity.
authors.affiliation: Duncan Guthrie Institute of Medical Genetics, Glasgow, Yorkhill, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Ong
authors.forename: W G
authors.initials: WG
authors.lastname: Lanyon
authors.forename: G
authors.initials: G
authors.lastname: Graham
authors.forename: R J
authors.initials: RJ
authors.lastname: Hift
authors.forename: J
authors.initials: J
authors.lastname: Halkett
authors.forename: M R
authors.initials: MR
authors.lastname: Moore
authors.forename: J M
authors.initials: JM
authors.lastname: Connor
mesh_terms: D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D017118:Porphyria, Acute Intermittent / Q000201:enzymology* / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013019:South Africa
chemical_list: D011994:Recombinant Proteins; D011163:Hydroxymethylbilane Synthase