A Novel Point Mutation of the Splicing Donor Site in the Intron 2 of the Plasmin Inhibitor Gene

Haruhiko Yoshinaga; Shinsaku Hirosawa; Dong Hui Chung; Nobuyuki Miyasaka; Nobuo Aoki; Remi Favier

doi:10.1055/s-0037-1614012

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2000; 84(02): 307-311
DOI: 10.1055/s-0037-1614012

Review Article

Schattauer GmbH

A Novel Point Mutation of the Splicing Donor Site in the Intron 2 of the Plasmin Inhibitor Gene

Haruhiko Yoshinaga

¹From the First Department of Internal Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

,

Shinsaku Hirosawa

¹From the First Department of Internal Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

,

Dong Hui Chung

¹From the First Department of Internal Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

,

Nobuyuki Miyasaka

¹From the First Department of Internal Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

,

Nobuo Aoki

¹From the First Department of Internal Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

,

Remi Favier

²Laboratory of Hematology and Hemostasis, Hospital Armand Trousseau, Paris, France

› Institutsangaben

Abstract

Summary

Plasmin inhibitor (PI) is a major physiological inhibitor of plasminmediated 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.

Keywords

Plasmin inhibitor - mutation - fibrinolysis - splicing donor site

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Referenzen

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