c.301C>T (p.Arg101Cys): A novel mutation in the thrombin-sensitive region of protein S associated with a dysfunctional protein

Franca Franchi; Ylenia Viscardi; Cristina Razzari; Elena m. Faioni; Paola Bonara; Eugenia Biguzzi; Pier Mannuccio Mannucci

doi:10.1160/TH06-01-0053

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(03): 381-383
DOI: 10.1160/TH06-01-0053

Case Report

Schattauer GmbH

c.301C>T (p.Arg101Cys): A novel mutation in the thrombin-sensitive region of protein S associated with a dysfunctional protein

Franca Franchi

¹A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan and Department of Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy

,

Ylenia Viscardi

¹A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan and Department of Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy

,

Cristina Razzari

¹A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan and Department of Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy

,

Elena m. Faioni

²Hematology and Thrombosis Unit, Ospedale San Paolo, DMCO University of Milan, Milan, Italy

,

Paola Bonara

³Department of Internal Medicine, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, University of Milan, Milan, Italy

,

Eugenia Biguzzi

¹A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan and Department of Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy

,

Pier Mannuccio Mannucci

¹A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan and Department of Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy

› Author Affiliations

Abstract

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References

References
1 Dahlback B, Stenflo J. High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein. Proc Natl Acad Sci USA 1981; 78: 2512-16.
2 Saller F, Villoutreix BO, Amelot A. et al. The γ-car- boxyglutamic acid domain of anticoagulant proteinS is involved in activated protein C cofactor activity, independently of phospholipid binding. Blood 2005; 105: 122-30.
3 He X, Shen L, Villoutreix BO. et al. Amino acid residues in thrombin-sensitive region and first epidermal growth factor domain of vitamin K-dependent protein S determining specificity of the activated proteinC cofactor function. J Biol Chem 1998; 273: 27449-58.
4 Mille-Baker B, Rezende SM, Simmonds RE. et al. Deletion or replacement of the second EGF-like domain of proteinS results in loss of APC cofactor activity. Blood 2003; 101: 1416-8.
5 Gandrille S, Borgel D, Sala N. et al. ProteinS deficiency: a database of mutations -summary of the first update; for the Plasma Coagulation Inhibitors Subcommettee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 2000; 84: 918.
6 Biguzzi E, Razzari C, Lane DA. et al. Protein S Italian Team. Molecular diversity and thrombotic risk in protein S deficiency: the PROSIT study. Hum Mutat 2005; 25: 259-69.
7 Hayashi T, Nishiota J, Shigekiyo T, Saito S, Suzuki K. Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S. Blood 1994; 83: 683-90.
8 Kimura R, Honda S, Kawasaki T. et al. Protein S-K196E mutation as a genetic risk factor for deep vein thrombosis in Japanese patients. Blood 2006; 107: 1737-8.
9 Giri TK, Garcia de Frutos P, Dahlback B. ProteinS Thr103Asn mutation associated with type II deficiency reproduced in vitro and functionally characterized. Thromb Haemost 2000; 84: 413-9.
10 Faioni EM, Valsecchi C, Palla A. et al. Free protein S deficiency is a risk factor for venous thrombosis. Thromb Haemost 1997; 78: 1343-6.
11 Espinosa-Parrilla Y, Yamazaki T, Dahlback B, Garcia de Frutos P. ProteinS secretion differences of missense mutants account for phenotypic heterogeneity. Blood 2000; 95: 173-6.
12 Giri TK, Garcia de Frutos P, Yamazaki T. et al. In vitro characterization of two naturally occuring mutations in the Thrombin-sensitive region of anticoagulant protein S. Thromb Haemost 1999; 82: 1627-33.
13 Rezende SM, Lane DA, Zoller B. et al. Genetic and phenotypic variability between families with hereditary protein S deficiency. Thromb Haemost 2002; 87: 258-65.
14 Rezende SM, Lane DA, Mille-Baker B. et al. Protein S Gla-domain mutations causing impaired Ca++-induced phospholipid binding and severe functional proteinS deficiency. Blood 2002; 100: 2812-9.
15 Long G, Lu D, Xie RL, Kalafatis M. Human protein S cleavage and inactivation by coagulation factor X. J Biol Chem 1998; 273: 11521-6.
16 Borgel D, Gaussem P, Garbay C. et al. Implication of proteinS thrombin-sensitive region with membrane binding via conformational changes in the gamma-carboxyglutamic acid-rich domain. Biochem J 2001; 360: 499-506.
17 Saller F, Kabache T, Aiach M. et al. The protein S thrombin-sensitive region modulates phospholipid binding and the γ-carboxyglutamic acid-rich (Gla) domain conformation ina non-specific manner. J Thromb Haemost 2006; 04: 704-6.
18 Smirnov MD, Safa O, Regan L. et al. A chimeric proteinC containing the prothrombin Gla domain exhibits increased anticoagulant activity and altered phospholipid specificity. J Biol Chem 1998; 273: 9031-40.