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Three case reports of inherited antithrombin deficiency in China: double novel missense mutations, a nonsense mutation and a frameshift mutation

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Abstract

Antithrombin is a plasma protein critical to the regulation of coagulation. It plays a pivotal anticoagulant role by preventing the activation of procoagulant proteinases. Inherited and (or) acquired deficiency of AT is an established risk factor for venous thromboembolism. Sequencing analysis of SERPINC1 gene of three families revealed that Family I had double novel missense mutations (c.134G > A&c.342T > G), Family II had a nonsense mutation (c.770G > A) while Family III had a frameshift mutation (c.800-803del). In addition, all of them had a large number of carriers in their families what was very rare in China.

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References

  1. Steven T, Olson, Benjamin Richard et al. (2010) Molecular mechanisms of antithrombin-heparin regulation of blood clotting proteinases A paradigm for understanding proteinase regulation by serpin family protein proteinase inhibitors. Biochimie 92:1587–1596

  2. Huntington JA (2006) Shape-shifting serpins-advantages of a mobile mechanism. Trends Bilchem Sci 31:427–435

    Article  CAS  Google Scholar 

  3. Maclean PS, Tait RC et al (2007) Hereditary and acquired antithrombin deficiency. Epidemiology pathogenesis and treatment options. Drugs 67:1429–1440

    Article  PubMed  CAS  Google Scholar 

  4. Quinsey NS, Greedy AL, Bottomley SP (2004) Molecules in focus antithrombin: in control of coagulation. Int J Biochem Cell Biol 36:386–389

    Article  PubMed  CAS  Google Scholar 

  5. Yamada H, Hoshi N, Kato EH et al (2000) Novel mutation (E113X) of antithrombin III gene (AT3) in a woman with gestational recurrent thrombosis. Am J Med Genet 91:348

    Article  PubMed  CAS  Google Scholar 

  6. Yi Gu, Qi Hua Fu (2011) Advances in antithrombin. Chin J Thromb Hemost 17:1

    Article  Google Scholar 

  7. Janssen HL, Meinardi JR, Vleggaar FP, van Uum SH, Haagsma EB et al (2000) Factor V Ledin mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study. Blood 96:2364–2368

    PubMed  CAS  Google Scholar 

  8. Kim H-J, Kim D-K et al (2008) Severe protein C deficiency from compound heterozygous mutations in the PROC gene in two Korean adult patients. Thromb Res 123:412–417

    Article  PubMed  CAS  Google Scholar 

  9. Lee BB, Viuavicencio L, Viuavicencio L, Kim Yw, Do YS, Koh KC, Lim HK et al (2006) Primary Bubb-Chiari syndrome: outcome of endovascular management for suprahepatic venous obstruction. J Vas Surg 43:101–108

    Article  Google Scholar 

  10. Okuda H, Yamagata H, Obata H, Lwata H, Sasaki R, lmai F et al (1995) Epidemiological and clinical features of Budd-Chiari syndrome in Japan. J Hepatol 22:1–9

    Article  PubMed  CAS  Google Scholar 

  11. Bhattacharyya M, Makharia G, Kaman M, Ahmed RP, Gupa PK, Saxena R (2004) Inherited prothrombotic defects in Budd-Chiari syndrome and portal vein thrombosis: a study from north India. Am J Clin Pathol 121:844–847

    Article  PubMed  Google Scholar 

  12. Zhang F, Zhuang J-H et al. (2010) Blood coagulation determination of the patients with membrane of inferior vena cava of Budd Chiarri syndrome. Chin J Curr Adv Gen Surg 13:4

    Google Scholar 

  13. Okuda K, Kage M, Shrestha SM et al (1998) Proposal of a new nomenclature for Budd-Chiaria syndrome: hepatic vein thrombosis versus thrombosis of the inferior vena cava at its hepatic portion. Hepatology 28(4):1191–1197

    Article  PubMed  CAS  Google Scholar 

  14. Zhang D-L, Yang N, et al. (2008) A study of coagulation and anticoagulation changes in liver cirrhosis patients with and without portal vein thrombosis. Chin J Pract Internal Med 28(6):459–461

    Google Scholar 

  15. Richard B, Swanson R, Schedin-Weiss S et al (2008) Characterization of the conformational alterations, reduced anticoagulant activity, and enhanced antiangiogenic activity of prelatent antithrombin. J Biologic Chem 283(21):14417–14429

    Article  CAS  Google Scholar 

  16. Zhang W, Chuang YI, Swanson R et al (2004) Antiangiogenic antithrombin down regulates the expression of the proangiogenic heparan sulfate proteoglycan, perlecan in endothelial cell. Blood 103:1185–1191

    Article  PubMed  CAS  Google Scholar 

  17. Zhang W, Swanson R, Xiong Y et al (2006) Antiangiogentic antithrombin blocks the heparan sulfate-dependent binding of proangiogentic growth factors to their endothelial cell receptors. J Biol Chem 1281:37302–37310

    Article  Google Scholar 

  18. Zhang WQ, Chuang YJ, Jin TQ et al (2006) Antiangiogentic antithrombin induces global changes in the gene expression profile of endothelial cell. Cancer Res 66:5047–5055

    Article  PubMed  CAS  Google Scholar 

  19. Sophia SW, Richard B, Hjelm R et al (2008) Antiangiogentic forms of antithrombin specifically bind to the anticoagulant heparin sequence. Biochemistry 47(51):13610–13619

    Article  Google Scholar 

Download references

Acknowledgments

We are grateful to the patients and their families’ members for their participation in this study. This work was supported by Key Discipline Project of Renji Hospital, Shanghai JiaoTong University School of Medicine (RJ4101309).

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Authors and Affiliations

  1. Department of Vascular Surgery, Shanghai JiaoTong University School of Medicine Renji Hospital, Shanghai, 200127, People’s Republic of China

    Haoyu Deng, Jiwei Zhang & Lan Zhang

  2. Department of Clinical Laboratory, Shanghai JiaoTong University School of Medicine Renji Hospital, Shanghai, 200127, People’s Republic of China

    Wei Shen & Yi Gu

  3. Department of Gastroenterology, Shanghai JiaoTong University School of Medicine Renji Hospital, Shanghai, 200127, People’s Republic of China

    Xiong Ma

Authors
  1. Haoyu Deng
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  2. Wei Shen
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  3. Yi Gu
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  4. Xiong Ma
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  5. Jiwei Zhang
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  6. Lan Zhang
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Correspondence to Lan Zhang.

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Deng, H., Shen, W., Gu, Y. et al. Three case reports of inherited antithrombin deficiency in China: double novel missense mutations, a nonsense mutation and a frameshift mutation. J Thromb Thrombolysis 34, 244–250 (2012). https://doi.org/10.1007/s11239-012-0733-7

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