Antithrombin deficiency in three Japanese families: One novel and two reported point mutations in the antithrombin gene

作者：Maruyama Keiko; Morishita Eriko^*; Karato Megumi; Kadono Tadaaki; Sekiya Akiko; Goto Yukie; Sato Tomomi; Nomoto Haruka; Omi Wataru; Tsuzura Sachie; Imai Hidenori; Asakura Hidesaku; Ohtake Shigeki; Nakao Shinji

来源：Thrombosis Research, 2013, 132(2): E118-E123.

DOI：10.1016/j.thromres.2013.06.001

• Antithrombin deficiency
• factor Xa inhibition activity assay
• thrombin inhibition activity assay

Introduction: Inherited antithrombin (AT) deficiency is associated with a predisposition to familial venous thromboembolic disease. We analyzed the AT gene in three unrelated patients with an AT deficiency who developed thrombosis. %26lt;br%26gt;Materials and Methods: We analyzed the SERPINC1 gene in three patients. Additionally, we expressed the three mutants in the COS-1 cells and compared their secretion rates and levels of AT activity with those of the wild-type (WT). %26lt;br%26gt;Results: We identified three distinct heterozygous mutations of c.2534C%26gt;T: p.56Arginine -%26gt; Cysteine (R56C), c.13398C%26gt;A: p.459Alanine -%26gt; Aspartic acid (A459D) and c.2703C%26gt;G: p.112 Proline -%26gt; Arginine (P112R). In the in vitro expression experiments, the AT antigen levels in the conditioned media (CM) of the R56C mutant were nearly equal to those of WT. In contrast, the AT antigen levels in the CM of the A459D and P112R mutants were significantly decreased. The AT activity of R56C was decreased in association with a shorter incubation time in a FXa inhibition assay and a thrombin inhibition-based activity test. However, the AT activity of R56C was comparable to that of WT when the incubation time was increased. %26lt;br%26gt;Conclusions: We concluded that the R56C mutant is responsible for type II HBS deficiency. We considered that the A459D and P112R mutants can be classified as belonging to the type I AT deficiency.

• 出版日期2013-8