title: Molecular analysis of porphobilinogen (PBG) deaminase gene mutations in acute intermittent porphyria: first study in patients of Slavic origin.
abstract: Acute intermittent porphyria (AIP) is an autosomally dominant inherited metabolic disorders caused by decreased activity of porphobilinogen deaminase, the third enzyme in the human heme biosynthetic pathway. We report here the first mutations in the human porphobilinogen deaminase gene in seven unrelated patients from the Czech and Slovak Republics with acute intermittent porphyria. We used denaturing gradient gel electrophoresis to screen all 15 exons and exon/intron boundaries of the porphobilinogen deaminase gene. Polymerase chain reaction products of abnormal migration patterns were subjected to direct sequencing to identify the causative mutations. Thus we revealed four novel mutations and three which have been previously described. Of the four novel mutations, two were mis-sense (G24S, V267M), one was a single base insertion (158insA) that produced a stop codon 12 codons downstream, and one was a single base substitution in intron 12 (771 + 1) resulting in a splicing defect. The three previously detected mutations were mis-sense mutations (R26C, R26H, G111R). These results suggest a high allelic heterogeneity in Czech and Slovak patients.
authors.affiliation: Department of Paediatrics, Faculty of Medicine I, Charles University, Prague, Czech Republic.
authors.forename: R
authors.initials: R
authors.lastname: Rosipal
authors.forename: H
authors.initials: H
authors.lastname: Puy
authors.forename: J
authors.initials: J
authors.lastname: Lamoril
authors.forename: P
authors.initials: P
authors.lastname: Martasek
authors.forename: Y
authors.initials: Y
authors.lastname: Nordmann
authors.forename: J C
authors.initials: JC
authors.lastname: Deybach
mesh_terms: D000622:Aminolevulinic Acid / Q000652:urine; D018153:Czech Republic; D005091:Exons; D005820:Genetic Testing; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000097:blood / Q000235:genetics*; D007438:Introns; D009154:Mutation; D011162:Porphobilinogen / Q000652:urine; D017118:Porphyria, Acute Intermittent / Q000097:blood / Q000235:genetics* / Q000652:urine; D018154:Slovakia
chemical_list: D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D011163:Hydroxymethylbilane Synthase