Using a thrombosis susceptibility panel, we screen nephropathic cystinosis patients who develop PTC as well as control nephropathic cystinosis patients without PTC. The panel includes 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). In patients with severe homocysteinemia (greater than or equal to 100 micro mol/l), we screen for the FV Leiden mutation, FV G1628A polymorphism, FV R2 allele, prothrombin 20210 mutation, and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms. To date, we have recruited five patients with PTC 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 (a shortened TT demonstrates an acceleration of fibrin monomer polymerization, which contributes to thrombotic tendency). Activated protein C resistance is a condition that leads to a hypercoagulable state with an increased risk for venous thrombosis; the IgM isotype of ACA has been shown to be associated with venous thrombosis. Thus, there appears to be no single risk factor for the development of PTC in the patients studied.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2007
Total Cost
$250,771
Indirect Cost
City
State
Country
United States
Zip Code
Ifon, Ekwere T; Pang, Alan L Y; Johnson, Warren et al. (2005) U94 alters FN1 and ANGPTL4 gene expression and inhibits tumorigenesis of prostate cancer cell line PC3. Cancer Cell Int 5:19
Raygada, M; Rennert, O (2005) Congenital generalized lipodystrophy: profile of the disease and gender differences in two siblings. Clin Genet 67:98-101
Ohta, Shoichiro; Lai, Edwin W; Pang, Alan L Y et al. (2005) Downregulation of metastasis suppressor genes in malignant pheochromocytoma. Int J Cancer 114:139-43
Corrigan, Emily C; Raygada, Margarita J; Vanderhoof, Vien H et al. (2005) A woman with spontaneous premature ovarian failure gives birth to a child with fragile X syndrome. Fertil Steril 84:1508
Dogulu, Cigdem F; Tsilou, Ekaterini; Rubin, Benjamin et al. (2004) Idiopathic intracranial hypertension in cystinosis. J Pediatr 145:673-8
Dogulu, Cigdem F; Kansu, Tulay; Leung, Michael Y K et al. (2003) Evidence for genetic susceptibility to thrombosis in idiopathic intracranial hypertension. Thromb Res 111:389-95