Three novel missense mutations in the antithrombin III (AT3) gene causing recurrent venous thrombosis - PubMed (original) (raw)

Three novel missense mutations in the antithrombin III (AT3) gene causing recurrent venous thrombosis

D S Millar et al. Hum Genet. 1994 Nov.

Abstract

The polymerase chain reaction and direct sequencing were used to determine the nature of the mutations in the antithrombin III (AT3) gene in seven unrelated patients with familial antithrombin III (ATIII) deficiency and recurrent venous thrombosis. Three novel mutations were found, two associated with a type I deficiency state (Pro80-->Thr and His120-->Tyr) manifesting reduced synthesis of ATIII. The other novel lesion (Met251-->Ile) was associated with a dysfunctional ATIII protein (type II ATIII deficiency) and is predicted to interfere either with a heparin-induced conformational change in the ATIII molecule or with docking to thrombin. A novel polymorphism (Tyr158-->Cys) was also found to occur in several individuals of Scandinavian origin.

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