MUTATION REPORTA case of deficiency of plasma plasminogen activator inhibitor-1 related to Ala15Thr mutation in its signal peptideZhang, Zi Yan; Wang, Zhao Yue; Dong, Ning Zheng; Bai, Xia; Zhang, Wei; Ruan, Chang GengAuthor Information Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. Sponsorship: This study was supported in part by a grant to Z.Y.W. from the National Science Foundation of China, Beijing, China (number 38970343). Correspondence and requests for reprints to Zhaoyue Wang, M.D., Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, 96 Shizi Street, Suzhou 215006, China. Tel: +86 512 65223637; fax: +86 512 65228072; e-mail: email@example.com Received 28 June 2004 Revised 18 August 2004 Accepted 7 October 2004 Blood Coagulation & Fibrinolysis: January 2005 - Volume 16 - Issue 1 - p 79-84 Buy Abstract The patient was a 34-year-old man with life-long bleeding episodes, whose hemorrhage problem was characterized predominately by prolonged bleeding at surgical or traumatic sites. All routine coagulation parameters were within normal ranges. The patient's bleeding tendency was not caused by factor XIII deficiency, α2-antiplasmin deficiency, or tissue type-plasminogen activator increase. His characteristic abnormalities of fibrinolysis included shortened euglobulin clot lysis time, low plasminogen activator inhibitor-1 (PAI-1) activity and antigen in plasma, which were remarkably reduced to only about 10% of control. An operation was performed in order to clear two hematomas in the patient's left leg and hip, and subsequent bleeding episodes were well controlled with adjuvant administration of intravenous aminomethylbenoic acid after surgery. PAI-1 gene analysis by polymerase chain reaction product sequencing revealed that the patient had a heterozygous missense mutation G to A transition at nucleotide position 4497 in exon 2, causing replacement of alanine 15 (GCC) to threonine (ACC) at signal peptide. The restriction endonuclease analysis showed that this gene mutation also existed in the patient's father, but not in his mother and 60 normal subjects. The wild-type and mutant plasmids were constructed and transiently transfected into Chinese hamster ovary cell lines; the levels of PAI-1 activity and antigen in the media of the mutant were approximately 70% of the wild type, and the levels of PAI-1 protein in cell lysates were almost equal in wild-type and mutant plasmids. These results indicate that the mutation in signal peptide may partly impair the secretion of PAI-1. © 2005 Lippincott Williams & Wilkins, Inc.