title: CRIM-positive mutations of acute intermittent porphyria in Finland.
abstract: Acute intermittent porphyria (AIP) is a dominantly inherited metabolic disease caused by a partial deficiency of the third enzyme, porphobilinogen deaminase (PBGD), in the heme biosynthetic pathway. AIP has been divided into two subtypes according to the ratio of enzyme polypeptide concentration and enzyme activity measured in erythrocytes: cross-reacting immunologic material (CRIM) positive or negative. In this study six out of the seven known CRIM-positive AIP families in Finland were analyzed and two also previously identified mutations in the PBGD gene were found to be responsible for AIP in this genetically isolated population. The search for mutations was focused on exon 10 based on previously found mutations. SSCP analysis revealed a known polymorphism but the two mutations in that region were found only by direct sequencing of the PCR products. A G518-->A substitution changing Arg173 to Gln was found in three families and a C499-->T substitution changing Arg167 to Trp was detected in three families. DNA analyses of the family members revealed that conventional assays of erythrocyte PBGD activity identified correctly only 72% of the carriers for the AIP mutation.
authors.affiliation: Third Department of Medicine, University Central Hospital of Helsinki, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Kauppinen
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
authors.forename: H
authors.initials: H
authors.lastname: Pihlaja
authors.forename: P
authors.initials: P
authors.lastname: Mustajoki
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003429:Cross Reactions; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005387:Finland; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics* / Q000276:immunology; D007438:Introns; D008969:Molecular Sequence Data; D017118:Porphyria, Acute Intermittent / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*
chemical_list: D004247:DNA; D011163:Hydroxymethylbilane Synthase