ACUTE INTERMITTENT PORPHYRIA - RAPID MOLECULAR DIAGNOSIS

Acute intermittent porphyria (AIP) is an autosomal dominant disorder c aused by a partial porphobilinogen (PBG) deaminase deficiency. An exon -by-exon denaturing gradient gel electrophoresis (DGGE) analysis follo wed by direct sequencing of the DNA fragments was performed to investi gate molecular defect in 8 unrelated patients living in south of Franc e: one Algerian, two Moroccan and five French patients. We have optimi zed the DGGE method in order to study at the same time the fifteen exo ns of the PEG deaminase gene in only one electrophoresis run. Six diff erent mutations were detected by abnormal mobility patterns. After cha racterization, a C insertion (716 ins C), 2 deletions (589 del 17 bp; 730 del CT), a non-sense mutation (R149X) and 2 missense mutations (A2 70G; R173W) were found. The R173W missense mutation was found in 3 unr elated patients, and 716 ins C, 589 del 17 bp and A270G were newly des cribed. According to this small AIP samples, sensitivity of the DGGE s creening method was 100%.