3 NOVEL MISSENSE MUTATIONS IN THE ANTITHROMBIN-III (AT3) GENE CAUSINGRECURRENT VENOUS THROMBOSIS

The polymerase chain reaction and direct sequencing were used to deter mine the nature of the mutations in the antithrombin III (AT3) gene in seven unrelated patients with familial antithrombin III (ATIII) defic iency and recurrent venous thrombosis. Three novel mutations were foun d, two associated with a type I deficiency state (Pro80-->Thr and His1 20-->Tyr) manifesting reduced synthesis of ATIII. The other novel lesi on (Met251-->Ile) was associated with a dysfunctional ATIII protein (t ype IT ATIII deficiency) and is predicted to interfere either with a h eparin-induced conformational change in the ATIII molecule or with doc king to thrombin. A novel polymorphism (Tyr158-->Cys) was also found t o occur in several individuals of Scandinavian origin.