Fibrinogen Saint-Germain II: Hypofibrinogenemia due to heterozygous γ N345S mutation

Emmanuelle de Raucourt; Philippe de Mazancourt; Ghassan J. Maghzal; Stephen O. Brennan; Michael W. Mosesson

doi:10.1160/TH05-05-0334

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(05): 965-968
DOI: 10.1160/TH05-05-0334

Blood Coagulation, Fibrnolysis and Cellular Haemostasis

Schattauer GmbH

Fibrinogen Saint-Germain II: Hypofibrinogenemia due to heterozygous γ N345S mutation

Emmanuelle de Raucourt

¹Laboratoire d’Hématologie, CHI Poissy-St-Germain-en-Laye, St-Germain-en-Laye, France

,

Philippe de Mazancourt

²Laboratoire de Biochimie et Biologie Moléculaire, Hôpital Poincaré, Garches France

,

Ghassan J. Maghzal

³Canterbury Health Laboratories, Christchurch, New Zealand

,

Stephen O. Brennan

³Canterbury Health Laboratories, Christchurch, New Zealand

,

Michael W. Mosesson

⁴Blood Research Institute, Blood Center of Wisconsin, Milwaukee, Wisconsin, USA

› Author Affiliations

Abstract

Summary

We have identified a novel heterozygous fibrinogen γ chain mutation, γN345S (Fibrinogen Saint-Germain II), in a subject with hypofibrinogenemia. There was no evidence by mass spectrometry of plasma fibrinogen containing the mutant chain. The hypofibrinogenemia was discovered in a 26-year-old man who experienced extensive deep venous thrombosis of the left leg associated with pulmonary embolism. Investigation of potential thromboembolic risk factors revealed heterozygosity of the factor V R506Q mutation (factor V Leiden) and heterozygosity of the prothrombin gene G20210A mutation. The hypofibrinogenemia may be contributory to the thrombophilic manifestations.

Keywords

Hypofibrinogenemia - thrombosis risk factors

Full Text

References

References
1 Mosesson MW, Siebenlist KR, Meh DA. The structure and biological features ofibrinogen and fibrin. Nieuwenhuizen W, Mosesson MW, de Maat MPM. editors. Fibrinogen. Ann NY Acad Sci 2001; 936: 11-30.
2 Mosesson MW. Fibrinogen gamma chain functions. J Thromb Haemost 2003; 1: 231-8.
3 Mosesson MW. Hereditary Fibrinogen Abnormalities. Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U. editors. Williams Hematology.. New York: McGraw-Hill.; 2005
4 Mosesson MW. Antithrombin I. Inhibition of thrombin generation in plasma by fibrin formation. Thromb Haemost 2003; 89: 9-12.
5 Clauss A. Rapid physiological coagulation method in determination of fibrinogen. Acta Haematol 1957; 17: 237-6.
6 Bertina RM, Koeleman PC, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
7 Raoul M, Mathonnet F, Peltier JY. et al. An improved method for the detection of the G20210A transition in the prothrombin gene. Thromb Res 1997; 88: 441-3.
8 Mosesson MW, Sherry S. The preparation and properties of human fibrinogen of relatively high solubility. Biochemistry 1966; 5: 2829-35.
9 Brennan SO. Electrospray ionisation analysis of human fibrinogen. Thromb Haemost 1997; 78: 1055-8.
10 Nelson C, Noelkan M, Buckley C, Tanford C, Hill R. Biochemistry. 1965; 4: 1418-26.
11 Meyer M, Franke K, Richter W. et al. New molecular defects in the gamma subdomain of fibrinogen D-domain in four cases of (hypo)dysfibrinogenemia: fibrinogen variants Hannover VI, Homburg VII, Stuttgart and Suhl. Thromb Haemost 2003; 89: 637-46.
12 Brennan SO, Wyatt J, Medicina D. et al. Fibrinogen brescia: hepatic endoplasmic reticulum storage and hypofibrinogenemia because of a gamma284 Gly–>Arg mutation. Am J Pathol 2000; 157: 189-96.
13 Brennan SO, Maghzal G, Shneider BL. et al. Novel fibrinogen gamma375 Arg–>Trp mutation (fibrinogen Aguadilla) causes hepatic endoplasmic reticulum storage and hypofibrinogenemia. Hepatology 2002; 36: 652-8.
14 Brennan SO, Wyatt JM, Fellowes AP. et al. Gamma371 Thr–>Ile substitution in the fibrinogen gamma D domain causes hypofibrinogenaemia. Biochim Biophys Acta 2001; 1550: 183-8
15 Brennan SO, Wyatt JM, May S. et al. Hypofibrinogenemia due to novel 316 Asp –> Tyr substitution in the fibrinogen Bbeta chain. Thromb Haemost 2001; 85: 450-3.
16 Brennan SO, Fellowes AP, Faed JM. et al. Hypofibrinogenemia in an individual with 2 coding (gamma82 A–>G and Bbeta235 P–>L) and 2 noncoding mutations. Blood 2000; 95: 1709-13
17 Wyatt J, Brennan SO, May S. et al. Hypofibrinogenaemia with compound heterozygosity for two gamma chain mutations – gamma 82 Ala–>Gly and an intron two GT->AT splice site mutation. Thromb Haemost 2000; 84: 449-52
18 Caen J, Faur Y, Inceman S. et al. Nécrose ischémique bilatérale dans un cas de grande hypofibrinogénémie congénitale. Nouv Rev Fr Hématol 1964; 4: 321-6.
19 Marchal G, Duhamel G, Samama M. et al. Thrombose massive des vaisseaux d’un membre au cours d’une hypofibrinémie congénitale. Hémostase 1964; 4: 81-9.
20 Nilsson IM, Niléhn J-E, Cronberg S. et al. Hypofibrinogenemia and massive thrombosis. Acta Medica Scandinavica 1966; 180: 65-76.
21 Ingram GI, McBrien DJ, Spencer H. Fatal pulmonary embolism in congenital fibrinopenia. Acta Haematol 1966; 35: 56-62.
22 Chafa O, Chellali T, Sternberg C. et al. Severe hypofibrinogenemia associated with bilateral ischemic necrosis of toes and fingers. Blood Coagul Fibrinolysis 1995; 6: 549-52.
23 Olds RJ, Fitches AC, Geary CPM. The multigenic basis for venous thrombosis. 2000. Br J Haematol 2000; 109: 508-11
24 Siebenlist KR, Mosesson MW, Meh DA. et al. Coexisting dysfibrinogenemia (gammaR275C) and factor V Leiden deficiency associated with thromboembolic disease (fibrinogen Cedar Rapids). Blood Coagul Fibrinolysis 2000; 11: 293-304.
25 Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen. Thromb Haemost 1995; 73: 151-61.