Familial thrombophilia: a complex genetic disorder.
Familial thrombosis has long been considered as an autosomal dominant trait, caused by a dominant gene defect with a reduced penetrance for the disease. Recently, this view has changed and today familial thrombophilia is considered as a complex genetic disorder caused by the segregation of two or more gene defects (known and unknown) in a family. Here we briefly discuss the known genetic defects (protein C, protein S, and antithrombin deficiency and activated protein C resistance associated with factor V Leiden) with special focus on the relation between gene mutation and plasma abnormality and on the association between abnormality and thrombosis in affected families and in the population. Finally, the evidence is reviewed that indicates familial thrombosis as an oligogenetic disorder and on the basis of these data strategies are discussed for the identification of new genetic risk factors for thrombosis via a genetic approach.
Koeleman
B P
BP
Haemostasis and Thrombosis Research Centre, University Hospital Leiden, The Netherlands.
Reitsma
P H
PH
Bertina
R M
RM
D000990:Antithrombin III / Q000235:genetics / Q000502:physiology; D020152:Antithrombin III Deficiency; D005165:Factor V / Q000235:genetics / Q000502:physiology; D005192:Family Health; D006801:Humans; D011486:Protein C / Q000235:genetics / Q000502:physiology; D017293:Protein S / Q000235:genetics / Q000502:physiology; D013924:Thrombophlebitis / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D013927:Thrombosis / Q000097:blood / Q000235:genetics*
D011486:Protein C; D017293:Protein S; C095381:factor V Leiden; D000990:Antithrombin III; D005165:Factor V