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Factor VI359T: a novel mutation associated with thrombosis and resistance to activated protein C

Mumford, AD; McVey, JH; Morse, CV; Gomez, K; Steen, Mårten LU ; Norström, Eva LU ; Tuddenham, EGD; Dahlbäck, Björn LU and Bolton-Maggs, PHB (2003) In British Journal of Haematology 123(3). p.496-501
Abstract
We report a kindred in which two siblings suffered spontaneous venous thromboses in the second decade of life. Further investigation showed reduced coagulation factor V (FV) activity and activated protein C resistance (APCR) ratio but no other thrombophilic abnormalities. The reduction in APCR ratio persisted in a modified APCR assay in which FV activity was normalized between test and control plasmas. Analysis of the FV gene showed that the thrombotic individuals had a complex genotype that included two novel point mutations c.529G>T and c.1250T>C resulting in FV E119X and FV I359T substitutions inherited on different alleles. Individuals in the kindred with FV E119X or FV I359T substitutions alone were asymptomatic. We suggest that... (More)
We report a kindred in which two siblings suffered spontaneous venous thromboses in the second decade of life. Further investigation showed reduced coagulation factor V (FV) activity and activated protein C resistance (APCR) ratio but no other thrombophilic abnormalities. The reduction in APCR ratio persisted in a modified APCR assay in which FV activity was normalized between test and control plasmas. Analysis of the FV gene showed that the thrombotic individuals had a complex genotype that included two novel point mutations c.529G>T and c.1250T>C resulting in FV E119X and FV I359T substitutions inherited on different alleles. Individuals in the kindred with FV E119X or FV I359T substitutions alone were asymptomatic. We suggest that the FV I359T substitution confers pro-thrombotic risk and APCR, but that this is only clinically manifest when co-inherited with the FV E119X allele. The FV I359T substitution creates a new consensus sequence for N-linked glycosylation within the FV heavy chain and we speculate that this abnormal glycosylation may disrupt activated protein C-mediated proteolysis of the variant FV and FVa. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
thrombosis, factor V, mutation, activated protein C resistance
in
British Journal of Haematology
volume
123
issue
3
pages
496 - 501
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:14617013
  • wos:000186048600019
  • scopus:0242329725
ISSN
0007-1048
DOI
10.1046/j.1365-2141.2003.04624.x
language
English
LU publication?
yes
id
e7c23697-0ff2-44af-a3d1-7f4611e23e96 (old id 298093)
date added to LUP
2007-09-18 14:16:59
date last changed
2018-01-14 03:28:38
@article{e7c23697-0ff2-44af-a3d1-7f4611e23e96,
  abstract     = {We report a kindred in which two siblings suffered spontaneous venous thromboses in the second decade of life. Further investigation showed reduced coagulation factor V (FV) activity and activated protein C resistance (APCR) ratio but no other thrombophilic abnormalities. The reduction in APCR ratio persisted in a modified APCR assay in which FV activity was normalized between test and control plasmas. Analysis of the FV gene showed that the thrombotic individuals had a complex genotype that included two novel point mutations c.529G>T and c.1250T>C resulting in FV E119X and FV I359T substitutions inherited on different alleles. Individuals in the kindred with FV E119X or FV I359T substitutions alone were asymptomatic. We suggest that the FV I359T substitution confers pro-thrombotic risk and APCR, but that this is only clinically manifest when co-inherited with the FV E119X allele. The FV I359T substitution creates a new consensus sequence for N-linked glycosylation within the FV heavy chain and we speculate that this abnormal glycosylation may disrupt activated protein C-mediated proteolysis of the variant FV and FVa.},
  author       = {Mumford, AD and McVey, JH and Morse, CV and Gomez, K and Steen, Mårten and Norström, Eva and Tuddenham, EGD and Dahlbäck, Björn and Bolton-Maggs, PHB},
  issn         = {0007-1048},
  keyword      = {thrombosis,factor V,mutation,activated protein C resistance},
  language     = {eng},
  number       = {3},
  pages        = {496--501},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {Factor VI359T: a novel mutation associated with thrombosis and resistance to activated protein C},
  url          = {http://dx.doi.org/10.1046/j.1365-2141.2003.04624.x},
  volume       = {123},
  year         = {2003},
}