Pinotti Mirko, Camire Rodney M, Baroni Marcello, Rajab Anna, Marchetti Giovanna, Bernardi Francesco
Department of Biochemistry and Molecular Biology, University of Ferara, Ferrara, Italy.
Thromb Haemost. 2003 Feb;89(2):243-8.
We investigated three members of a large Omani family affected by severe factor X (FX) deficiency (coagulant activity <1%) and showing marked differences in the onset of severe hemorrhagic symptoms. All patients were homozygous for a novel FX mutation (Gly381Asp) in the structurally conserved region of the serine protease active site. Expression levels of recombinant 381D-FX were similar to those of wt-FX, indicating the presence of a severe CRM+ FX deficiency, a poorly investigated condition. The 381D-FX was normally activated and did not show a detectable amidolytic activity. Instead, we observed a residual activity in a prothrombin-time based assay (1%) and in prothrombinase assays both in plasma (1%) and in purified systems (3%). Comparison with FX variants characterized by reduced activation suggests that mutations affecting FX activity might result in a more pronounced impairment of coagulation and thus in severe hemorrhagic phenotype. In addition, this study indicates that the hemorrhagic heterogeneity observed in FX deficiencies is only partially explained by molecular analysis of FX gene.
我们研究了一个受严重因子X（FX）缺乏症影响的大型阿曼家族中的三名成员（凝血活性<1%），他们在严重出血症状的发作方面表现出显著差异。所有患者在丝氨酸蛋白酶活性位点的结构保守区域均为一种新型FX突变（Gly381Asp）的纯合子。重组381D - FX的表达水平与野生型FX相似，表明存在严重的交叉反应物质阳性（CRM +）FX缺乏症，这是一种研究较少的情况。381D - FX正常激活且未显示出可检测到的酰胺水解活性。相反，我们在基于凝血酶原时间的检测中观察到残余活性（1%），在血浆中的凝血酶原酶检测（1%）以及纯化系统中的检测（3%）中也观察到残余活性。与以激活减少为特征的FX变体进行比较表明，影响FX活性的突变可能导致凝血功能更明显的损害，从而导致严重的出血表型。此外，本研究表明，在FX缺乏症中观察到的出血异质性仅部分可通过FX基因的分子分析来解释。
