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Human Genetics

, Volume 102, Issue 5, pp 541–548 | Cite as

Three splicing defects, an insertion, and two missense mutations responsible for acute intermittent porphyria

  • S. Mustajoki
  • Hannele Pihlaja
  • Helena Ahola
  • Niels Erik Petersen
  • Pertti Mustajoki
  • Raili Kauppinen
Original investigation

Abstract

Three splicing defects (IVS1+3G→T, 86A→T, IVS13–2A→G), an insertion (416insCA), and two missense mutations (664G→A and 833T→G) in the porphobilinogen deaminase (PBGD) gene were identified in six unrelated Finnish patients with acute intermittent porphyria (AIP). The IVS1+3G→T substitution resulted in activation of a cryptic splice site in intron 1 and retention of a 67-bp fragment in the mutant transcript. The 86A→T mutation at the end of exon 3 was predicted to cause an amino acid substitution (E29L). However, sequencing of the cDNA sample of the proband revealed exon 3 skipping from the mutant transcript. The IVS13–2A→G substitution caused retention of intron 13 in the mutant transcript. In exon 8, 416insCA resulted in a frameshift. All three splicing defects and the CA insertion resulted in a truncated protein and thus, probably the loss of PBGD activity. The two novel missense mutations, 664G→A in exon 12 and 833T→C in exon 14 caused a single amino acid substitution (V222M and L278P). So far 25 different mutations have been characterized from 37 (93%) of a total of 40 unrelated Finnish AIP families, confirming the genetic heterogeneity of the disease even in a previously isolated area of Finland.

Keywords

Missense Mutation Amino Acid Substitution Splice Site Genetic Heterogeneity Single Amino Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • S. Mustajoki
    • 1
  • Hannele Pihlaja
    • 1
  • Helena Ahola
    • 1
  • Niels Erik Petersen
    • 2
  • Pertti Mustajoki
    • 1
  • Raili Kauppinen
    • 1
  1. 1.Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, P.O.BOX 340, FIN-00029 HYKS, Helsinki, Finland e-mail: sami.mustajoki@helsinki.fi, Tel.: +3589 471 2324, Fax: +3589 471 4012FI
  2. 2.Department of Clinical Chemistry, Odense University Hospital, DK-5000 Odense C, DenmarkDK

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