title: A novel point mutation of the splicing donor site in the intron 2 of the plasmin inhibitor gene.
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.
authors.affiliation: First Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshinaga
authors.forename: S
authors.initials: S
authors.lastname: Hirosawa
authors.forename: D H
authors.initials: DH
authors.lastname: Chung
authors.forename: N
authors.initials: N
authors.lastname: Miyasaka
authors.forename: N
authors.initials: N
authors.lastname: Aoki
authors.forename: R
authors.initials: R
authors.lastname: Favier
mesh_terms: D000818:Animals; D000933:Antifibrinolytic Agents / Q000378:metabolism; D019556:COS Cells; D018388:Codon, Terminator; D003593:Cytoplasm / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D017354:Point Mutation / Q000235:genetics* / Q000502:physiology; D021382:Protein Sorting Signals / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000979:alpha-2-Antiplasmin / Q000172:deficiency / Q000235:genetics*
chemical_list: D000933:Antifibrinolytic Agents; D018388:Codon, Terminator; D021382:Protein Sorting Signals; D022821:RNA Splice Sites; D012333:RNA, Messenger; D000979:alpha-2-Antiplasmin; C418194:plasmin Paris-Trousseau