Original Investigations

Human Genetics

, Volume 90, Issue 1, pp 12-16

First online:

Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA

  • C. S. MgoneAffiliated withDuncan Guthrie Institute of Medical Genetics
  • , W. G. LanyonAffiliated withDuncan Guthrie Institute of Medical Genetics
  • , M. R. MooreAffiliated withPorphyria Research Unit, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary
  • , J. M. ConnorAffiliated withDuncan Guthrie Institute of Medical Genetics

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Direct cDNA sequencing has been performed on asymmetrically amplified transcripts from the human porphobilinogen deaminase gene. Lymphocytes from 30 patients with acute intermittent porphyria were the source of mRNA; of the seven separate point mutations detected, three were silent, whereas four resulted in amino acid changes. Three of these changes involved highly conserved amino acids, and the remaining one a conserved charge. One of these mutations was predicted to cause structural alterations in the protein product. The application of this method to affected families allows the direct identification of these heterogeneous mutations, thus permitting the unequivocal detection of carriers.