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

Plasmin inhibitor (PI) is a major physiological inhibitor of plasmin-mediat ed fibrinolysis; hence, its deficiency results in a severe haemorrhagic dia thesis. We analyzed the PI gene of a French boy apparently homozygous for P I deficiency and his heterozygous parents. Both alleles of the homozygous p atient had a novel G to A transition at the consensus splicing donor site i n the intron 2 of the PI gene. In an expression assay using the heterologou s cells transfected with the mutant PI expression vector, 3 types of aberra nt 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 spli cing site and encode only 25 amino acids, comprising the first 21 amino aci ds of the signal peptide (27 amino acids) plus 4 new amino acids. This muta nt was designated as PI-Paris-Trousseau.