Acute intermittent porphyria in a native North American family. Biochemical and molecular analysis

A native North American family with acute intermittent porphyria was investigated by molecular methods to locate the causative mutation and identify carriers of the mutant allele. All 15 exons of the porphobilinogen deaminase gene were screened by single-strand conformation polymorphism analysis, and a unique banding pattern was observed in exon 14. Sequencing revealed a one base-pair insertion in this exon that shifts the reading frame of the mRNA, and generates a premature stop codon. Family members were tested for the mutation by amplification of exon 14 followed by digestion with the restriction enzyme NlaIII. The activity of erythrocyte porphobilinogen deaminase was measured in 36 family members. The results agreed with mutational analysis in 32 cases. However, four individuals who were not gene carriers had low enzyme activity, and in the absence of molecular genetic data would have been incorrectly diagnosed. This is the first study to identify the molecular basis of acute intermittent porphyria in native North Americans.