A novel point mutation of the splicing donor site in the intron 2 of the plasmin inhibitor gene

Thromb Haemost. 2000 Aug;84(2):307-11.

Abstract

Plasmin inhibitor (PI) is a major physiological inhibitor of plasmin-mediated fibrinolysis; hence, its deficiency results in a severe haemorrhagic diathesis. We analyzed the PI gene of a French boy apparently homozygous for PI deficiency and his heterozygous parents. Both alleles of the homozygous patient had a novel G to A transition at the consensus splicing donor site in the intron 2 of the PI gene. In an expression assay using the heterologous cells transfected with the mutant PI expression vector, 3 types of aberrant transcripts using a cryptic splicing donor site within the intron 2 were detected. All of these mRNAs had a stop codon upstream of the cryptic splicing site and encode only 25 amino acids, comprising the first 21 amino acids of the signal peptide (27 amino acids) plus 4 new amino acids. This mutant was designated as PI-Paris-Trousseau.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifibrinolytic Agents / metabolism
  • COS Cells
  • Codon, Terminator
  • Cytoplasm / genetics
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Gene Expression
  • Heterozygote
  • Homozygote
  • Humans
  • Introns / genetics
  • Male
  • Point Mutation / genetics*
  • Point Mutation / physiology
  • Protein Sorting Signals / genetics
  • RNA Splice Sites / genetics*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • alpha-2-Antiplasmin / deficiency
  • alpha-2-Antiplasmin / genetics*

Substances

  • Antifibrinolytic Agents
  • Codon, Terminator
  • Protein Sorting Signals
  • RNA Splice Sites
  • RNA, Messenger
  • alpha-2-Antiplasmin
  • plasmin Paris-Trousseau