FRAMESHIFT MUTATIONS IN EXON-9 AND EXON-20 OF THE PORPHOBILINOGEN DEAMINASE GENE PRODUCE A CROSS-REACTING IMMUNOLOGICAL MATERIAL (CRIM)-NEGATIVE FORM OF ACUTE INTERMITTENT PORPHYRIA

Single-strand conformation polymorphism analysis was used to screen al l 15 exons of the porphobilinogen deaminase gene from 13 patients with acute intermittent porphyria. Unique banding patterns in two amplifie d gene fragments, one containing exon 9 and another containing exon 10 , were further investigated. Sequence analysis of cloned genomic DNA r evealed a single base pair insertion in the middle of exon 9 in one pa tient and a single base pair deletion near the 3' end of exon 10 in tw o related patients. Both mutations change the reading frame of the mRN A transcript and predict proteins that are normal at their NH2-termina l ends but contain novel, unrelated sequences at their COOH-terminal e nds and are prematurely terminated. Frameshift mutations in the porpho bilinogen deaminase gene are uncommon; this is the first report of an insertion mutation causing acute intermittent porphyria.