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Thromb Haemost 2001; 85(01): 82-87
DOI: 10.1055/s-0037-1612908
Review Article
Schattauer GmbH

Genetic Screening of Candidate Genes for a Prothrombotic Interaction with Type I Protein C Deficiency in a Large Kindred

Bruce T. Scott
1   Department of Pathology, University of Utah, Salt Lake City, UT, USA
,
Edwin G. Bovill
1   Department of Pathology, University of Utah, Salt Lake City, UT, USA
,
Peter W. Callas
2   Biometry Facility, University of Utah, Salt Lake City, UT, USA
,
Sandra J. Hasstedt
4   Human Genetics, University of Utah, Salt Lake City, UT, USA
,
Mark F. Leppert
4   Human Genetics, University of Utah, Salt Lake City, UT, USA
,
Julia E. Valliere
1   Department of Pathology, University of Utah, Salt Lake City, UT, USA
,
Tena S. Varvil
4   Human Genetics, University of Utah, Salt Lake City, UT, USA
,
G. L. Long
3   Department of Biochemistry, University of Vermont, Burlington, VT, USA
› InstitutsangabenSupported 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.
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Publikationsverlauf

Received 18. Februar 2000

Accepted after revision 06. Juni 2000

Publikationsdatum:
08. Dezember 2017 (online)

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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.

Keywords

Protein C - thrombophilia
 

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