Identification of five novel mutations in the porphobilinogen deaminase gene

We have studied the porphobilinogen deaminase gene transcripts from seven unrelated patients from the West of Scotland, all suffering from acute intermittent porphyria. This was achieved by reverse transcription and PCR amplification of mRNA followed by asymmetric amplification and direct sequencing. Five novel and two previously described mutations were identified and found to be single base substitutions. Of the five novel mutations, three were missense (R116Q, T2691, G274R) and two were nonsense (Q204 Stop, W283 Stop). Using Escherichia coli PBGD as a model, it is possible to predict and explain the deleterious effects that these mutations might have on the function and structure of the enzyme