Two novel mutations in the prothrombin gene cause severe bleeding in a compound heterozygous patient

Hypoprothrombinemia is a rare hereditary coagulation defect characterized b y low levels of biologically active prothrombin. In this paper we report th e laboratory and genetic analysis of a patient with a severe hypoprothrombi nemia and some of her relatives. Laboratory analysis showed very low levels of prothrombin antigen. Molecular analysis of the prothrombin genes of the patient resulted in the identification of two novel sequence variations in heterozygous state, a 20079 G to A transition, which predicts a Trp 569--> Stop mutation, and a 1261C-->G change within intron B near the acceptor spl ice site. A cosegregation of prothrombin deficiency in family members with the two genetic defects was observed. (C) 1998 Lippincott Williams & Wilkin s.