© 1994 Oxford University Press
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Identification of five novel mutations in the porphobilinogen deaminase gene
Duncan Guthrie Institute of Medical Genetics Yorkhbl, Glasgow G3 8SJ 1Porphyna Research Unit, University Department of Medicine and Therapeutics Gardiner Institute, Western Infirmary, Glasgow G11 6NT 2Laboratory of Molecular Biology, Department of Crystallography and Imperial Cancer Research Fund, Structural Molecular Biology Unit, Birkbeck College, University of London Malet Street, London WC1E, UK
* To whom correspondence should be addressed at present address: Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, EHP, Papua New Guinea
Received November 29, 1993; Accepted February 25, 1994
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 Escherichla coll 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.