Thrombosis from a prothrombin mutation conveying antithrombin resistance.
نویسندگان
چکیده
We identified a novel mechanism of hereditary thrombosis associated with antithrombin resistance, with a substitution of arginine for leucine at position 596 (p.Arg596Leu) in the gene encoding prothrombin (called prothrombin Yukuhashi). The mutant prothrombin had moderately lower activity than wild-type prothrombin in clotting assays, but the formation of thrombin-antithrombin complex was substantially impaired. A thrombin-generation assay revealed that the peak activity of the mutant prothrombin was fairly low, but its inactivation was extremely slow in reconstituted plasma. The Leu596 substitution caused a gain-of-function mutation in the prothrombin gene, resulting in resistance to antithrombin and susceptibility to thrombosis.
منابع مشابه
New Prothrombin Mutation (Arg596Trp, Prothrombin Padua 2) Associated With Venous Thromboembolism.
OBJECTIVE Two different prothrombin variants, p.Arg596Leu and p.Arg596Gln, conferring antithrombin resistance to patients with venous thromboembolism have been recently reported. Here, we describe a novel substitution affecting Arg596 of prothrombin molecule (Arginine596 to Tryptophan or p.Arg596Trp or Arg221aTrp in the chymotrypsinogen numbering system or prothrombin Padua 2) in 2 Italian fami...
متن کاملFactor V Leiden, MTHFR C677T and Prothrombin Gene Mutation G20210A in Iranian Patients with Venous Thrombosis
Background: Factor V Leiden, Prothrombin gene (G20210A) and MTHFR (C677T) polymorphism are the main biomarkers for evaluation of tendency for venous thromboembolism. We aimed to investigate the frequency of mutations in factor V Leiden, Prothrombin G20210A and MTHFR C677T and identify the genetic status for these mutations in patients with venous thrombosis. Methods: This study was carried out...
متن کاملFactor V Leiden and other coagulation factor mutations affecting thrombotic risk.
Five genetic defects have been established as risk factors for venous thrombosis. Three are protein C, protein S, and antithrombin deficiencies, defects in the anticoagulant pathways of blood coagulation. Together they can be found in approximately 15% of families with inherited thrombophilia. Their laboratory diagnosis is hampered by the large genetic heterogeneity of these defects. The other ...
متن کاملProthrombin G20210A gene mutation and further prothrombotic risk factors in childhood thrombophilia.
Risk factors for venous thrombosis in adults are the prothrombin G20210A and the factor V (FV) G1691A mutations and hereditary deficiencies of protein C, protein S and antithrombin. However, data are limited on the relevance of these risk factors for thrombosis in children and adolescents. We therefore investigated 261 patients aged 0 to 18 (median 5.7 years, 48% male) with venous thrombosis an...
متن کاملTreatment of deep vein thrombosis from Iranian traditional medicine and modern medicine points of view: comparative study
Background and objectives: Recently, deep vein thrombosis (DVT) has remained a major cause of morbidity and death. DVT is a serious public health issue and can be complicated by pulmonary embolism and stroke leading to high economic burden. Disease etiologies may include protein C deficiency, protein S deficiency, factor V Leiden gene mutation, prothrombin gene 20210A mutation,...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The New England journal of medicine
دوره 366 25 شماره
صفحات -
تاریخ انتشار 2012