title: Two novel mutations in the prothrombin gene cause severe bleeding in a compound heterozygous patient.
abstract: Hypoprothrombinemia is a rare hereditary coagulation defect characterized by low levels of biologically active prothrombin. In this paper we report the laboratory and genetic analysis of a patient with a severe hypoprothrombinemia 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 splice site. A cosegregation of prothrombin deficiency in family members with the two genetic defects was observed.
authors.affiliation: Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical School, The Netherlands.
authors.forename: S R
authors.initials: SR
authors.lastname: Poort
authors.forename: K T
authors.initials: KT
authors.lastname: Njo
authors.forename: H L
authors.initials: HL
authors.lastname: Vos
authors.forename: R M
authors.initials: RM
authors.lastname: Bertina
mesh_terms: D000328:Adult; D000483:Alleles; D018388:Codon, Terminator; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006470:Hemorrhage / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007020:Hypoprothrombinemias / Q000235:genetics*; D008297:Male; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011516:Prothrombin / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018388:Codon, Terminator; D011516:Prothrombin