TY - JOUR
T1 - A novel mutation in the F5 gene (factor V Amsterdam) associated with bleeding independent of factor V procoagulant function
AU - Cunha, Marisa L. R.
AU - Bakhtiari, Kamran
AU - Peter, Jorge
AU - Marquart, J. Arnoud
AU - Meijers, Joost C. M.
AU - Middeldorp, Saskia
PY - 2015
Y1 - 2015
N2 - We investigated a small Dutch family with a bleeding diathesis, prolonged prothrombin, and activated partial thromboplastin times, in whom no classifying diagnosis was made. The 2 affected relatives had severely decreased in vitro thrombin generation, and levels of tissue factor pathway inhibitor (TFPI) were strongly increased. To identify the genetic cause of the bleeding diathesis, we performed whole exome sequencing analysis of all living relatives. We found a novel gain-of-function mutation in the F5 gene (c.C2588G), which leads to an aberrant splicing of F5 and ultimately to a short factor V protein (missing 623 amino acids from the B domain), which we called factor V Amsterdam. Factor V Amsterdam binds to TFPI, prolonging its half-life and concentration. This is the second report of an association between a shorter form of factor V and increased TFPI levels, resulting in severely reduced thrombin generation and a bleeding tendency
AB - We investigated a small Dutch family with a bleeding diathesis, prolonged prothrombin, and activated partial thromboplastin times, in whom no classifying diagnosis was made. The 2 affected relatives had severely decreased in vitro thrombin generation, and levels of tissue factor pathway inhibitor (TFPI) were strongly increased. To identify the genetic cause of the bleeding diathesis, we performed whole exome sequencing analysis of all living relatives. We found a novel gain-of-function mutation in the F5 gene (c.C2588G), which leads to an aberrant splicing of F5 and ultimately to a short factor V protein (missing 623 amino acids from the B domain), which we called factor V Amsterdam. Factor V Amsterdam binds to TFPI, prolonging its half-life and concentration. This is the second report of an association between a shorter form of factor V and increased TFPI levels, resulting in severely reduced thrombin generation and a bleeding tendency
U2 - https://doi.org/10.1182/blood-2014-08-592733
DO - https://doi.org/10.1182/blood-2014-08-592733
M3 - Article
C2 - 25634741
SN - 0006-4971
VL - 125
SP - 1822
EP - 1825
JO - Blood
JF - Blood
IS - 11
ER -