Acute intermittent porphyria: rapid molecular diagnosis

Abstract

Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial porphobilinogen (PBG) deaminase deficiency. An exon-by-exon denaturing gradient gel electrophoresis (DGGE) analysis followed by direct sequencing of the DNA fragments was performed to investigate molecular defect in 8 unrelated patients living in south of France: one Algerian, two Moroccan and five French patients. We have optimized the DGGE method in order to study at the same time the fifteen exons of the PBG deaminase gene in only one electrophoresis run. Six different mutations were detected by abnormal mobility patterns. After characterization, a C insertion (716 ins C), 2 deletions (589 del 17 bp; 730 del CT), a non-sense mutation (R149X) and 2 missense mutations (A270G; R173W) were found. The R173W missense mutation was found in 3 unrelated patients, and 716 ins C, 589 del 17 bp and A270G were newly described. According to this small AIP samples, sensitivity of the DGGE screening method was 100%.