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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2018, Vol. 12 Issue (3) : 319-323    https://doi.org/10.1007/s11684-017-0553-4
CASE REPORT |
Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism: a case report
Dong Wang, Min Tian, Guanglin Cui(), Dao Wen Wang
Institute of Hypertension and Department of Internal Medicine, Division of Cardiology, Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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Abstract

Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in SERPINC1 and PROC lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of PROC and SERPINC1 were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in SERPINC1 and a short deletion variant c.572_574delAGA in PROC. This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the SERPINC1 and PROC gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.

Keywords antithrombin deficiency      protein C activity      mutation      variant      venous thromboembolism      anticoagulants     
Corresponding Authors: Guanglin Cui   
Just Accepted Date: 26 July 2017   Online First Date: 08 November 2017    Issue Date: 04 May 2018
 Cite this article:   
Dong Wang,Min Tian,Guanglin Cui, et al. Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism: a case report[J]. Front. Med., 2018, 12(3): 319-323.
 URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0553-4
http://academic.hep.com.cn/fmd/EN/Y2018/V12/I3/319
Fig.1  Genetic analysis of the PROC and SERPINC1 gene in the family. Sequencing of PROC and SERPINC1 gene revealed that the patient carried both heterozygous deletion variant c.572_574delAGA of PROC and heterozygous small insertion c.848_849insGATGT of SERPINC1. Family study showed that PROC c.572_574delAGA inherited from his mother and SERPINC1 c.848_849insGATGT from his father; his brother inherited SERPINC1 c.848_849insGATGT from his father. The arrow indicated the proband.
Family memberAge (year)SERPINC1 c.848_849insGATGTPROC c.572_574delAGAAT:A (%)AT:Ag
(%)
PC:A (%)PC:Ag
(%)
PS:A
(%)
PS:Ag
(%)
VTE
Patient22+/-+/-4448819399100Yes
Father48+/--/-5852122106105106No
Mother45-/-+/-11010797101121134No
Brother23+/--/-4749108110132146No
Tab.1  Clinic and genetic characteristics of the family
Fig.2  Mutations of SERPINC1 (A) and PROC (B) genes reported in the Chinese population. The gray bars represent exons, and the horizontal black line between exons represents introns. Mutations are listed around the exons, the AT, PC antigen level, and activities, and the references of each mutation are shown in Tables S2 and S3.
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