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Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C

Zöller, Bengt LU ; Svensson, P J LU ; He, X and Dahlbäck, Björn LU (1994) In Journal of Clinical Investigation 94(6). p.2521-2524
Abstract

Resistance to activated protein C (APC) is the most prevalent inherited cause of venous thrombosis. The APC resistance phenotype is associated with a single point mutation in the factor V gene, changing Arg506 in the APC cleavage site to a Gln. We have investigated 50 Swedish families with inherited APC resistance for this mutation and found it to be present in 47 of them. Perfect cosegregation between a low APC ratio and the presence of mutation was seen in 40 families. In seven families, the co-segregation was not perfect as 12 out of 57 APC-resistant family members were found to lack the mutation. Moreover, in three families with APC resistance, the factor V gene mutation was not found, suggesting another still unidentified cause of... (More)

Resistance to activated protein C (APC) is the most prevalent inherited cause of venous thrombosis. The APC resistance phenotype is associated with a single point mutation in the factor V gene, changing Arg506 in the APC cleavage site to a Gln. We have investigated 50 Swedish families with inherited APC resistance for this mutation and found it to be present in 47 of them. Perfect cosegregation between a low APC ratio and the presence of mutation was seen in 40 families. In seven families, the co-segregation was not perfect as 12 out of 57 APC-resistant family members were found to lack the mutation. Moreover, in three families with APC resistance, the factor V gene mutation was not found, suggesting another still unidentified cause of inherited APC resistance. Of 308 investigated families members, 146 were normal, 144 heterozygotes, and 18 homozygotes for the factor V gene mutation and there were significant differences in thrombosis-free survival curves between these groups. By age 33 yr, 8% of normals, 20% of heterozygotes, and 40% of homozygotes had had manifestation of venous thrombosis.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
blood coagulation, factor V, protein C, protein S, thrombophilia, blood clotting factor 5, article, blood clotting, blood clotting disorder, controlled study, female, gene mutation, human, major clinical study, male, point mutation, priority journal, vein thrombosis
in
Journal of Clinical Investigation
volume
94
issue
6
pages
4 pages
publisher
The Journal of Clinical Investigation
external identifiers
  • scopus:0028037137
ISSN
0021-9738
DOI
10.1172/JCI117623
language
English
LU publication?
yes
id
a5e57d85-5750-4a1c-9ff1-5b9804ff72f0
date added to LUP
2017-10-19 16:35:33
date last changed
2017-11-07 14:15:02
@article{a5e57d85-5750-4a1c-9ff1-5b9804ff72f0,
  abstract     = {<p>Resistance to activated protein C (APC) is the most prevalent inherited cause of venous thrombosis. The APC resistance phenotype is associated with a single point mutation in the factor V gene, changing Arg506 in the APC cleavage site to a Gln. We have investigated 50 Swedish families with inherited APC resistance for this mutation and found it to be present in 47 of them. Perfect cosegregation between a low APC ratio and the presence of mutation was seen in 40 families. In seven families, the co-segregation was not perfect as 12 out of 57 APC-resistant family members were found to lack the mutation. Moreover, in three families with APC resistance, the factor V gene mutation was not found, suggesting another still unidentified cause of inherited APC resistance. Of 308 investigated families members, 146 were normal, 144 heterozygotes, and 18 homozygotes for the factor V gene mutation and there were significant differences in thrombosis-free survival curves between these groups. By age 33 yr, 8% of normals, 20% of heterozygotes, and 40% of homozygotes had had manifestation of venous thrombosis.</p>},
  author       = {Zöller, Bengt and Svensson, P J and He, X and Dahlbäck, Björn},
  issn         = {0021-9738},
  keyword      = {blood coagulation,factor V,protein C,protein S,thrombophilia,blood clotting factor 5,article,blood clotting,blood clotting disorder,controlled study,female,gene mutation,human,major clinical study,male,point mutation,priority journal,vein thrombosis},
  language     = {eng},
  number       = {6},
  pages        = {2521--2524},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C},
  url          = {http://dx.doi.org/10.1172/JCI117623},
  volume       = {94},
  year         = {1994},
}