Factor V Leiden (FV R506Q) in Families with Inherited Antithrombin Deficiency

作者：Hester H. van Boven, Pieter H. Reitsma, Frits Richard Rosendaal, Trevor A. Bayston, Vijoy Chowdhury, Jeanne Yvonne Borg, Kenneth Alan Bauer, I. Scharrer, J. Conard, David A. Lane · 发表于：Thrombosis and Haemostasis · 年份：1996 · DOI：10.1055/s-0038-1650289 · 被引用次数：240 · 研究领域：Blood Coagulation and Thrombosis Mechanisms、Hemophilia Treatment and Research、Coagulation, Bradykinin, Polyphosphates, and Angioedema

We investigated the presence of the gene mutation of factor V, FV R506Q or factor V Leiden, responsible for activated protein C resistance, in DNA samples of 127 probands and 188 relatives from 128 families with antithrombin deficiency. The factor V mutation was identified in 18 families. Nine families were available to assess the mode of inheritance and the clinical relevance of combined defects. The factor V and antithrombin genes both map to chromosome 1. Segregation of the defects on opposite chromosomes was observed in three families. Co-segregation with both defects on the same chromosome was demonstrated in four families. In one family a de novo mutation of the antithrombin gene and in another a crossing-over event were the most likely explanations for the observed inheritance patterns. In six families with type I or II antithrombin deficiency (reactive site or pleiotropic effect), 11 of the 12 individuals with both antithrombin deficiency and the factor V mutation developed thrombosis. The median age of their first thrombotic episode was 16 years (range 0-19); this is low compared with a median age of onset of 26 years (range 20-49) in 15 of 30 carriers with only a defect in the antithrombin gene. One of five subjects with only factor V mutation experienced thrombosis at 40 years of age. In three families with type II heparin binding site deficiencies, two of six subjects with combined defects experienced thrombosis; one was homozygous for the heparin binding defect. ...