DETECTION OF 4 MUTATIONS IN 6 UNRELATED SOUTH-AFRICAN PATIENTS WITH ACUTE INTERMITTENT PORPHYRIA

We have screened the hydroxymethylbilane synthase cDNA from six South African patients with acute intermittent porphyria, using a combinatio n of chemical cleavage mismatch analysis and direct sequencing of asym metrically amplified PCR products. Four mutations were detected, a nov el T insertion (771insT) and three missense mutations (R26H, R116W and R173Q). The 771insT mutation produces a stop codon, thirty-three codo ns downstream and a loss of approximately 20% of the protein is predic ted. The R116W mutation, Which was found to have a high prevalence in the Dutch population, was detected in three unrelated South African pa tients. (C) 1996 Academic Press Limited