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DOI: 10.1055/s-0037-1612908
Genetic Screening of Candidate Genes for a Prothrombotic Interaction with Type I Protein C Deficiency in a Large Kindred
Supported in part by the Public Health Service National Heart, Lung and Blood institute, Grant No. P01 HL46703 “Surface dependent reactions in thrombosis and thrombolysis”, and University of Vermont General Clinical Research Center’s NIH Grant #RR00109.Publication History
Received
18 February 2000
Accepted after revision
06 June 2000
Publication Date:
08 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200101/lookinside/thumbnails/10-1055-s-0037-1612908-1.jpg)
Summary
The incomplete penetrance of thrombosis in familial protein C deficiency suggests disease occurs when this deficit is combined with additional abnormalities in the hemostatic system. The pattern of inherited thrombophilia in the Vermont II kindred, which is affected by a clinically dominant type I protein C deficiency, provides strong evidence for a second unidentified gene that segregates independently of protein C deficiency and increases susceptibility to thrombosis. To test the second gene hypothesis, thirty-four candidate genes for proteins involved in hemostasis or inflammation were tested as the unknown defect, using highly polymorphic short tandem repeat (STR) markers in an informative subset (n = 31) of the kindred. The genes considered are; α-fibrinogen, β-fibrinogen, γ-fibrinogen, prothrombin, tissue factor, factor V, protein S, complement component 4 binding protein, factor XI, factor XII, factor XIIIa, factor Xlllb, histidine rich glycoprotein, high molecular weight kininogen, kallikrein, von Willebrands factor, platelet factor 4, thrombospondin, antithrombin III, α-1-antitrypsin, thrombomodulin, plasminogen, tissue plasminogen activator, urokinase plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, protein C inhibitor, α-2-plasmin inhibitor, kallistatin, lipoprotein a, interleukin 6, interleukin 1, cystathionine-β-synthase, and methylenetetrahydrofolate reductase. Mutations in many of these genes have been previously established as independent risk factors for thrombosis. However, linkage analysis provided no evidence to implicate any of the candidate genes as the second inherited factor that promotes thrombophilia in this kindred.
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