Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acroangiodermatitis of Mali is a dermatologic condition of kaposiform skin lesions that has been associated with chronic venous insufficiency. Here we report a case of a 28-year-old Chinese man with acroangiodermatitis which co-existed with chronic lower limb deep vein thrombosis. Investigations revealed protein C deficiency and a frame shift mutation, c246_247dupCT, of the PROC gene. Our report lengthens the list of male acroangiodermatitis of Mali cases with a Chinese patient harboring a novel PROC mutation with manifest protein C deficiency.
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PMID:Acroangiodermatitis of Mali in protein C deficiency due to a novel PROC gene mutation. 2244 73

Genetic predisposition of thromboembolism depends on the racial background. Factor V Leiden (G1691A) and factor II mutation (G20210A) are the leading causes of inherited thrombophilias in Caucasians, but are not found in Asian ancestries. Protein S (PS), protein C (PC) and antithrombin (AT) activity are reportedly low in 65% of adult Japanese patients with deep vein thrombosis. Approximately half of the patients with each deficiency carry the heterozygous mutation of PS (PROS1; 20%), PC (PROC; 10%), and AT genes (SERPINC1: 5%). Recently, several studies have revealed an outline of inherited thrombophilias in Japanese children. Congenital thrombophilias in 48 patients less than age 20 years consisted of 45% PC deficiency, 15% PS deficiency and 10% AT deficiency, along with other causes. All PS- and AT-deficient patients had a heterozygous mutation of the respective gene. On the other hand, PC-deficient patients were considered to carry the homozygous or compound heterozygous mutation in 50%, the heterozygous mutation in 25%, and unknown causes in the remaining 25% of patients. Half of unrelated patients with homozygous or compound heterozygous PROC mutations carried PC-nagoya (1362delG), while their parents with its heterozygous mutation were asymptomatic. Most of the PC-deficient patients developed intracranial lesion and/or purpura fulminans within 2 weeks after birth. Non-inherited PC deficiency also conveyed thromboembolic events in early infancy. The molecular epidemiology of thrombosis in Asian children would provide a clue to establish the early intervention and optimal anticoagulant therapy in pediatric PC deficiency.
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PMID:Protein C deficiency as the major cause of thrombophilias in childhood. 2352 Oct 84

Protein C (PC) and protein S (PS) are vitamin K-dependent glycoproteins, that act as natural anticoagulants. The proteolytic activation of PC by thrombin occurs on the surface of endothelial cells and involves thrombomodulin and endothelial PC receptor. In the presence of PS, phospholipids and calcium, activated PC (APC) inactivates membrane bound factors V (FVa) and FVIIIa by their cleavage at the specific arginine residues. PC and PS deficiencies are inherited as autosomal dominant disorders associated with recurrent venous thromboembolism (VTE) and, in most cases, derived from heterozygous missense mutations (78% and 63%, respectively). Heterozygous PC deficiency is found in 6% of families with inherited thrombophilia, in 3% of patients with a first-time deep vein thrombosis (DVT) and 0.2-0.3% of healthy individuals. The PS deficiency is detected more commonly than PC deficiency and its prevalence has been estimated with a less than 0.5% in the general European population and 2% to 12% of selected groups of thrombophilic patients. Approximately 75% of PC-deficient patients have type I deficiency and 95% of PS-deficient patients develop type I and type III of PS deficiency. The diagnosis of PC and PS deficiencies is challenging, many preanalytical and analytical factors may affect the PC/PS levels. Molecular analysis of the PC and PS genes (PROC and PROS1, respectively) involves direct gene sequencing and if negative, multiplex ligation-dependent probe amplification (MLPA) method. Patients with low PC and PS levels and the known mutation within PROC or PROS1 genes combined with other genetic or environmental thrombosis factors are at increased risk of recurrent thromboembolic events and require lifelong oral anticoagulation.
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PMID:Protein C and protein S deficiency - practical diagnostic issues. 2398 5

Rare mutations in PROC, PROS1 or SERPINC1 as well as common variants in F5, F2, F11 and SERPINC1 have been identified as risk factors for deep vein thrombosis (DVT). To identify novel genetic risk factors for DVT, we have developed and applied next-generation DNA sequencing (NGS) of the coding area of hemostatic and proinflammatory genes. Using this strategy, we previously identified a single nucleotide variant (SNV) rs6050 in the FGA gene and novel, rare SNVs in the ADAMTS13 gene associated with DVT. To identify novel coding variants in the genetic predisposition to DVT, we applied NGS analysis of the coding area of 186 hemostatic and proinflammatory genes in 94 DVT cases and 98 controls and we identified 18 variants with putative role in DVT. A group of 585 Italian idiopathic DVT patients and 550 healthy controls was used to genotype all the 18 risk-associated variants identified by NGS. Replication study in the Italian population identified the rs2232710 variant in the protein Z-dependent protease inhibitor (ZPI) gene to be associated with an increased risk of DVT (OR 2.74; 95% CI 1.33-5.65; P = 0.0045; Bonferroni P = 0.081). However, the rs2232710 SNV showed no association with DVT in two Dutch replication cohorts the LETS study (454 patients and 451 controls) and the MEGA study (3799 patients and 4399 controls), indicating that the rs2232710 variant is not a risk factor for DVT.
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PMID:Single Nucleotide Variant rs2232710 in the Protein Z-Dependent Protease Inhibitor (ZPI, SERPINA10) Gene Is Not Associated with Deep Vein Thrombosis. 2698 41

Hereditary protein C (PC) deficiency is an autosomal dominant disorder associated with a high risk of venous thromboembolism (VTE). Here we report a case of inherited PC deficiency associated with recurrent deep venous thrombosis. Two mutations were revealed in PROC (c.1152C>G, p.N384K and c.1207G>T, p.G403W) by genetic testing. Results from this case suggest that the inherited PC deficiency due to the PROC mutations may cause recurrent VTE. Long-term anticoagulant therapy may be appropriate for these patients with recurrent VTE and hereditary PC deficiency.
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PMID:Protein C deficiency resulting from two mutations in PROC presenting with recurrent venous thromboembolism. 2934 39

: The current study aims to explore the phenotype and genotype of a mutation Ala291Thr, which responsible for type I protein C (PC) deficiency in a Chinese woman. The PROC antigen was tested with chromogenic substrate method. PROC gene were amplified by PCR with direct sequencing. Bioinformatics and model analysis were used to study the harm of the mutation. PC activity (PC: A) levels of three members were reduced to 39, 57 and 56%, respectively, PC: antigen was decreased parallelly same as PC: A. Sequencing analysis showed proband with a novel heterozygous c.997G>A point mutation in exon 9 of PROC gene resulting in Ala291Thr. The Ala291Thr mutation is responsible for the decrease of PC: A, which is cross-reacting material negative deficiency and the first reported in the world. This mutation alone may not have significant clinical symptoms, whereas it will cause deep vein thrombosis when combined with systemic lupus erythematosus.
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PMID:Protein C deficiency (a novel mutation: ala291Thr) with systemic lupus erythematosus leads to the deep vein thrombosis. 3043 69

Deep vein thrombosis and pulmonary embolism, collectively defined as venous thromboembolism (VTE), are the third leading cause of cardiovascular death in the United States. Common genetic variants conferring increased varying degrees of VTE risk have been identified by genome-wide association studies (GWAS). Rare mutations in the anticoagulant genes PROC, PROS1 and SERPINC1 result in perinatal lethal thrombosis in homozygotes and markedly increased VTE risk in heterozygotes. However, currently described VTE variants account for an insufficient portion of risk to be routinely used for clinical decision making. To identify new rare VTE risk variants, we performed a whole-exome study of 393 individuals with unprovoked VTE and 6114 controls. This study identified 4 genes harboring an excess number of rare damaging variants in patients with VTE: PROS1, STAB2, PROC, and SERPINC1. At STAB2, 7.8% of VTE cases and 2.4% of controls had a qualifying rare variant. In cell culture, VTE-associated variants of STAB2 had a reduced surface expression compared with reference STAB2. Common variants in STAB2 have been previously associated with plasma von Willebrand factor and coagulation factor VIII levels in GWAS, suggesting that haploinsufficiency of stabilin-2 may increase VTE risk through elevated levels of these procoagulants. In an independent cohort, we found higher von Willebrand factor levels and equivalent propeptide levels in individuals with rare STAB2 variants compared with controls. Taken together, this study demonstrates the utility of gene-based collapsing analyses to identify loci harboring an excess of rare variants with functional connections to a complex thrombotic disease.
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PMID:Whole-exome sequencing identifies rare variants in STAB2 associated with venous thromboembolic disease. 3245 82