当前位置： SCI文献检索 > THROMBOSIS AND HAEMOSTASIS期刊下所有文献 > Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency.

Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency.

Abstract：

: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. Our results show that, when thrombosis occurs at a young age in antithrombin deficiency, the factor V mutation is a likely additional risk factor. Co-segregation of mutations in the antithrombin and factor V genes provides a molecular explanation for severe thrombosis in several generations. The findings support that combinations of genetic risk factors underly differences in thrombotic risk in families with thrombophilia.

journal_name

Thromb Haemost

journal_title

Thrombosis and haemostasis

authors

van Boven HH,Reitsma PH,Rosendaal FR,Bayston TA,Chowdhury V,Bauer KA,Scharrer I,Conard J,Lane DA

subject

Has Abstract

pub_date

1996-03-01 00:00:00

pages

417-21

issue

eissn

0340-6245

issn

2567-689X

journal_volume

pub_type

杂志文章

在线工具

Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency.