title: A single thymine nucleotide deletion responsible for congenital deficiency of plasmin inhibitor.
abstract: Plasma plasmin inhibitor (PI) is a physiological inhibitor of plasmin-mediated fibrinolysis and constitutes a hemostatic component in blood plasma; hence its deficiency results in a severe hemorrhagic diathesis. We have carried out molecular analysis of American family members with congenital PI deficiency, and detected a single thymine deletion at nucleotide position 332 in exon 5. The deletion was found in both alleles of the homozygotes and in one allele of the heterozygotes, and the patterns of restriction fragment length polymorphism created by the mutation in the family members were compatible with their phenotypes. The deletion caused a frameshift leading to an alteration and shortening of the deduced amino acid sequence. The amino acid sequence consists of the first 83 amino acids of the N-terminal sequence of the normal PI and additional new amino acids, resulting in a mutant composed of 94 amino acids in contrast to 464 amino acids of the normal PI. In transient expression analysis, the mutant PI whose molecular size was compatible with the predicted amino acid sequence was detected in the lysates of the cells transfected with the mutated PI expression vector. The mutant PI was retained and underwent progressive degradation within the cells, and was minimally excreted into the media. These data indicate that this mutation is the cause of PI deficiency in this pedigree.
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshinaga
authors.forename: Masako
authors.initials: M
authors.lastname: Nakahara
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Koyama
authors.forename: Aya
authors.initials: A
authors.lastname: Shibamiya
authors.forename: Fumie
authors.initials: F
authors.lastname: Nakazawa
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Miles
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Hirosawa
authors.forename: Nobuo
authors.initials: N
authors.lastname: Aoki
mesh_terms: D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000302:isolation & purification; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D030342:Genetic Diseases, Inborn / Q000209:etiology / Q000235:genetics; D006474:Hemorrhagic Disorders / Q000209:etiology; D006801:Humans; D008297:Male; D008970:Molecular Weight; D010375:Pedigree; D013936:Thymidine; D000979:alpha-2-Antiplasmin / Q000172:deficiency* / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D000979:alpha-2-Antiplasmin; D013936:Thymidine