title: Detection of eleven mutations causing acute intermittent porphyria using denaturing gradient gel electrophoresis.
abstract: Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by mutations of the gene coding for porphobilinogen deaminase (PBGD). Until now, sixteen different mutations have been described. In an effort to investigate further the molecular epidemiology of AIP, we have undertaken a systematic study of different exons of the PBGD gene from a large number of unrelated patients. Here, we have examined seven of the fifteen exons of the gene from 43 unrelated Dutch and French AIP patients using denaturing gradient gel electrophoresis after polymerase chain reaction amplification. Eleven new mutations were found, accounting for the enzymatic defect in about half of the patients. This study further documents the molecular heterogeneity of the mutations responsible for AIP and describes an efficient strategy to detect the mutations in patients with previously unknown abnormalities.
authors.affiliation: Laboratoire de Génétique Moléculaire, Faculté Xavier Bichat, Paris, France.
authors.forename: X F
authors.initials: XF
authors.lastname: Gu
authors.forename: F
authors.initials: F
authors.lastname: de Rooij
authors.forename: G
authors.initials: G
authors.lastname: Voortman
authors.forename: K
authors.initials: K
authors.lastname: Te Velde
authors.forename: J C
authors.initials: JC
authors.lastname: Deybach
authors.forename: Y
authors.initials: Y
authors.lastname: Nordmann
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
mesh_terms: D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017118:Porphyria, Acute Intermittent / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D011163:Hydroxymethylbilane Synthase