Familial thrombophilia : clinical and molecular analysis of Swedish families with inherited resistance to activated protein C or protein S deficiency
Zöller, Bengt LU
(1996)
In Scandinavian journal of clinical and laboratory investigation. Supplementum
56(226).
p.19-46
- Abstract
This report describes the characterization of Swedish families with inherited resistance to activated protein C (APC resistance) and/or protein S deficiency, two genetic disorders associated with functional impairment of the protein C anticoagulant pathway. The APC resistance phenotype was linked to the factor V gene locus in a kindred with independent inheritance of APC resistance and protein S deficiency. A point mutation changing Arg506 to a Gln (FV:Q506) in the factor V gene was the cause of APC resistance. In studies of 50 families with hereditary APC resistance, the FV:Q506 mutation was identified in 94% (47/50) of the families, and the thrombotic risk was found to be dependent on the factor V genotype. Moreover, 18 families with... (More)
This report describes the characterization of Swedish families with inherited resistance to activated protein C (APC resistance) and/or protein S deficiency, two genetic disorders associated with functional impairment of the protein C anticoagulant pathway. The APC resistance phenotype was linked to the factor V gene locus in a kindred with independent inheritance of APC resistance and protein S deficiency. A point mutation changing Arg506 to a Gln (FV:Q506) in the factor V gene was the cause of APC resistance. In studies of 50 families with hereditary APC resistance, the FV:Q506 mutation was identified in 94% (47/50) of the families, and the thrombotic risk was found to be dependent on the factor V genotype. Moreover, 18 families with hereditary deficiency of free protein S were investigated. Type I protein S deficiency (low free and total protein S) and type III deficiency (low free but normal total protein S) coexisted in 78% (14/18) of the families, suggesting the two types to be phenotypic variants of the same genetic disorder. Deficiency of free protein S was caused by equimolar relationship between protein S and beta-chain containing isoforms of C4BP. Though protein S deficiency was a strong risk factor for thrombosis, the FV:Q506 mutation was identified as an additional genetic risk factor in 39% of the families. Thus, familial thrombophilia is a multiple gene disorder. The thrombophilic tendency associated with APC resistance or protein S deficiency was related to increased levels of prothrombin fragment 1 + 2, reflecting increased activation of the common coagulation pathway.
(Less)
- author
- Zöller, Bengt
LU
- organization
- publishing date
- 1996
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- activated protein C, blood clotting factor 5, familial disease, family, gene locus, heredity, human, phenotype, point mutation, priority journal, protein S deficiency, review, Sweden, thrombophilia
- in
- Scandinavian journal of clinical and laboratory investigation. Supplementum
- volume
- 56
- issue
- 226
- pages
- 28 pages
- publisher
- Taylor & Francis
- external identifiers
-
- scopus:0030478027
- pmid:8981666
- ISSN
- 0085-591X
- language
- English
- LU publication?
- yes
- id
- 36dc4028-65e0-4e74-992f-4413dea994e8
- date added to LUP
- 2017-10-19 15:24:20
- date last changed
- 2024-04-28 21:59:19
@article{36dc4028-65e0-4e74-992f-4413dea994e8,
abstract = {{<p>This report describes the characterization of Swedish families with inherited resistance to activated protein C (APC resistance) and/or protein S deficiency, two genetic disorders associated with functional impairment of the protein C anticoagulant pathway. The APC resistance phenotype was linked to the factor V gene locus in a kindred with independent inheritance of APC resistance and protein S deficiency. A point mutation changing Arg506 to a Gln (FV:Q506) in the factor V gene was the cause of APC resistance. In studies of 50 families with hereditary APC resistance, the FV:Q506 mutation was identified in 94% (47/50) of the families, and the thrombotic risk was found to be dependent on the factor V genotype. Moreover, 18 families with hereditary deficiency of free protein S were investigated. Type I protein S deficiency (low free and total protein S) and type III deficiency (low free but normal total protein S) coexisted in 78% (14/18) of the families, suggesting the two types to be phenotypic variants of the same genetic disorder. Deficiency of free protein S was caused by equimolar relationship between protein S and beta-chain containing isoforms of C4BP. Though protein S deficiency was a strong risk factor for thrombosis, the FV:Q506 mutation was identified as an additional genetic risk factor in 39% of the families. Thus, familial thrombophilia is a multiple gene disorder. The thrombophilic tendency associated with APC resistance or protein S deficiency was related to increased levels of prothrombin fragment 1 + 2, reflecting increased activation of the common coagulation pathway.</p>}},
author = {{Zöller, Bengt}},
issn = {{0085-591X}},
keywords = {{activated protein C; blood clotting factor 5; familial disease; family; gene locus; heredity; human; phenotype; point mutation; priority journal; protein S deficiency; review; Sweden; thrombophilia}},
language = {{eng}},
number = {{226}},
pages = {{19--46}},
publisher = {{Taylor & Francis}},
series = {{Scandinavian journal of clinical and laboratory investigation. Supplementum}},
title = {{Familial thrombophilia : clinical and molecular analysis of Swedish families with inherited resistance to activated protein C or protein S deficiency}},
volume = {{56}},
year = {{1996}},
}