Human Genetics

, Volume 85, Issue 6, pp 631–634 | Cite as

Acute intermittent porphyria caused by a C→T mutation that produces a stop codon in the porphobilinogen deaminase gene

  • G. A. Scobie
  • D. H. Llewellyn
  • A. J. Urquhart
  • S. J. Smyth
  • N. A. Kalsheker
  • P. R. Harrison
  • G. H. Elder
Original Investigations

Summary

A mutation of the porphobilinogen (PBG) deaminase gene that produces the cross-reacting immunological material (CRIM)-negative type of acute intermittent porphyria (AIP) has been identified in one of 43 unrelated patients with this form of the disorder. The mutation is a C→T transition that abolishes a PstI recognition site in exon 9 of the gene and converts a codon for glutamine to a stop codon.

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References

  1. Chretien S, Dubart A, Beaupain D, Raich N, Grandchamp B, Rosa J, Goossens M, Romeo P-H (1988) Alternative transcription and splicing of the human porphobilinogen deaminase gene result either in tissue-specific or in housekeeping expression. Proc Natl Acad Sci USA 85:6–10Google Scholar
  2. Desnick RJ, Ostasiewicz LT, Tishler PA, Mustajoki P (1985) Acute intermittent porphyria: characterization of a novel mutation in the structural gene for porphobilinogen deaminase. J Clin Invest 76:865–874Google Scholar
  3. Feinberg A, Vogelstein B (1983) A technique for labelling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13PubMedGoogle Scholar
  4. Grandchamp B, Verneuil M de, Beaumont C, Chretien S, Walter O, Nordmann Y (1987) Tissue-specific expression of porphobilinogen deaminase − two isoenzymes from a single gene. Eur J Biochem 162:105–110Google Scholar
  5. Grandchamp B, Picat C, Mignotte V, Wilson JHP, Velde K te, Sandkuyl L, Romeo PH, Goossens M, Nordmann Y (1989a) Tissue-specific splicing mutation in acute intermittent porphyria. Proc Natl Acad Sci USA 86:661–664Google Scholar
  6. Grandchamp B, Picat C, Rooij F de, Beaumont C, Wilson P, Deybach JC, Nordmann Y (1989b) A point mutation G→A in exon 12 of the porphobilinogen deaminase gene results in exon skipping and is responsible for acute intermittent porphyria. Nucleic Acids Res 17:6637–6648Google Scholar
  7. Grandchamp B, Picat C, Kauppinen R, Mignotte V, Peltonen L, Mustajoki P, Romeo PH, Goossens M, Nordmann Y (1989c) Molecular analysis of acute intermittent prophyria in a Finnish family with normal erythrocyte porphobilinogen deaminase. Eur J Clin Invest 19:415–418Google Scholar
  8. Kappas A, Sassa S, Galbraith RA, Nordmann Y (1989) The Porphyrias. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited diseases, 6th edn. McGraw-Hill, New York, pp 1305–1366Google Scholar
  9. Lee J-S, Anvret M, Lindsten J, Lannfelt L, Gellerfors P, Wetterberg L, Floderus Y, Thunell S (1988) DNA polymorphisms within the porphobilinogen deaminase gene in two Swedish families with acute intermittent porphyria. Hum Genet 79:379–381Google Scholar
  10. Llewellyn DH, Kalsheker NA, Harrison PR, Picat C, Romeo PH, Elder GH, Marsh OWM, Grandchamp B, Nordmann Y, Goossens M (1987) DNA polymorphism of human porphobilinogen deaminase gene in acute intermittent porphyria. Lancet II:706–708Google Scholar
  11. Llewellyn DH, Urquhart AJ, Scobie G, Elder GH, Kalsheker NA, Harrison PR (1988) Molecular analysis of acute intermittent porphyria. Biochem Soc Trans 16:799–800Google Scholar
  12. Miller AD, Hart GJ, Packman LC, Battersby AR (1988) Evidence that the pyrromethane cofactor of hydroxymethylbilane synthase (porphobilinogen deaminase) is bound to the protein through the sulphur atom of cysteine-242. Biochem J 254:915–918Google Scholar
  13. Newton CR, Kalsheker N, Graham A, Powell S, Gammack A, Riley J, Markham AF (1988) Diagnosis of α1-antitrypsin deficiency by enzymatic amplification of human genomic DNA nd direct sequencing of polymerase chain reaction products. Nucleic Acids Res 16:8233–8243Google Scholar
  14. Raich N, Romeo PH, Dubart A, Beaupain D, Cohen-Solal M, Goossens M (1986) Molecular cloning and complete primary sequence of human erythrocyte porphobilinogen deaminase. Nucleic Acids Res 14:5955–5968Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • G. A. Scobie
    • 1
  • D. H. Llewellyn
    • 1
  • A. J. Urquhart
    • 1
  • S. J. Smyth
    • 1
  • N. A. Kalsheker
    • 1
  • P. R. Harrison
    • 2
  • G. H. Elder
    • 1
  1. 1.Department of Medical BiochemistryUniversity of Wales College of MedicineHeath ParkUK
  2. 2.Beatson Institute for Cancer ResearchBearsdenUK

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