Identification of genetic susceptibility to thrombosis i

鉴于我们的研究结果有关遗传易感性血栓形成的假性脑肿瘤（PTC），我们正在研究血栓形成的作用，在发展中的PTC肾病胱氨酸病。我们通过使用血栓形成易感性面板筛选发展PTC的肾病性胱氨酸病患者和对照无PTC的肾病性胱氨酸病患者，血栓形成易感性面板包括凝血酶原时间（PT）、活化部分凝血活酶时间（aPTT）、凝血酶时间（TT）、活化蛋白C抗性（APCR）、蛋白C和S的血清水平、抗凝血酶III、纤维蛋白原、总同型半胱氨酸、抗磷脂抗体（ACA组和狼疮AC）和筛选FV Leiden突变、FV G1628A多态性、FV R2等位基因、凝血酶原20210突变和5，10-亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性与严重同型半胱氨酸血症（> 100 μ mol/l）的关系到目前为止，我们已经招募了五名患有假性脑瘤的患者，他们既有肾病性胱氨酸病。血栓形成筛查组显示2例患者凝血酶时间（TT）缩短，1例患者抗心磷脂（ACA）IgM抗体滴度升高，一名患者出现活化蛋白C耐药（APCR）。凝血酶时间测量纤维蛋白单体聚合的速率，并且是纤维蛋白原减少或异常的最灵敏的筛选试验。缩短的TT表明纤维蛋白单体聚合加速，导致血栓形成倾向。活化蛋白C抵抗是导致高凝状态的病症，其具有增加的静脉血栓形成风险，并且ACA的IgM同种型已显示与静脉血栓形成相关。 识别血栓形成倾向（MERT）的方法进展 Dogulu，Chan，Rennert，与Su合作 静脉血栓形成每年影响1/1000个体，并且是死亡和发病的主要原因之一，仅在美国每年就导致约300，000例住院和50，000例死亡。然而，如果采用现有的预防性治疗，这是一种可以避免的疾病。我们设计了一种方法（正在申请专利），通过快速、同时筛选8个不同基因中所有已知的143个静脉血栓形成相关复发突变和多态性，可以预测和准确评估几个种族人群中的遗传性血栓形成倾向，以制定风险适应性预防的分层方案。

Given our findings regarding genetic susceptibility to thrombosis in pseudotumor cerebri (PTC), we are studying the role of thrombosis in the development of PTC in nephropathic cystinosis. We are screening nephropathic cystinosis patients who develop PTC and control nephropathic cystinosis patients without PTC by using a thrombosis susceptibility panel including prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), activated protein C resistance (APCR), serum levels of protein C and S, antithrombin III, fibrinogen, total homocysteine, antiphospholipid antibodies (ACA panel and Lupus AC) and screening for FV Leiden mutation, FV G1628A polymorphism, FV R2 allele, Prothrombin 20210 mutation and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in patients with severe homocysteinemia (>100 micro mol/l). To date, we have recruited five patients with Pseudotumor Cerebri with pre-existing Nephropathic Cystinosis. The thrombosis screening panel revealed shortened thrombin time (TT) in two patients, high titer Anticardiolipin (ACA) IgM antibodies in one patient and. Activated Protein C Resistance (APCR) in one patient. Thrombin time measures the rate of fibrin monomer polymerization and is the most sensitive screening test for decreases or abnormalities in fibrinogen. The shortened TT demonstrates an acceleration of fibrin monomer polymerization leading to thrombotic tendency. Activated protein C resistance is a condition which leads to a hypercoagulable state with an increased risk for venous thrombosis and IgM isotype of ACA has been shown to be associated with venous thrombosis. Method Evolved for Recognition of Thrombophilia (MERT) Dogulu, Chan, Rennert, in collaboration with Su Venous thrombosis affects 1 per 1000 individuals annually and is one of the leading causes of mortality and morbidity resulting in approximately 300,000 hospitalizations and 50,000 fatalities per year in the United States alone. It is, however, an avoidable disease if currently available prophylactic treatment is instituted. We have devised an approach (patent pending) that will allow prediction and accurate assessment of hereditary thrombophilia in several ethnic populations by rapid, concurrent screening of an array of all known 143 venous thrombosis associated recurrent mutations and polymorphisms in 8 different genes in order to develop stratification protocols for risk-adapted prophylaxis.