A novel mutation (Ser951LeufsTer8) in F5 gene leads to hereditary coagulation factor V deficiency.
Journal
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
ISSN: 1473-5733
Titre abrégé: Blood Coagul Fibrinolysis
Pays: England
ID NLM: 9102551
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
pubmed:
15
1
2021
medline:
27
5
2021
entrez:
14
1
2021
Statut:
ppublish
Résumé
The current study aims to explore the phenotype and genotype of a novel mutation (Ser951LeufsTer8) of F5 gene combined with polymorphism (R485K) in a family of hereditary coagulation factor V deficiency. The factor V activity and antigen were tested with clotting assay and ELISA. The F5 gene was amplified by PCR with direct sequencing and TA-clone-sequenced. The protein structure and harmfulness of the mutation were studied by Swiss-PdbViewer and bioinformatics software. The prothrombin time and activated partial thromboplastin time of proband were significantly prolonged, factor V activity and factor V antigen both were reduced to less than 20%. Sequencing analysis detected proband with Ser951LeufsTer8 and R485K (Arg513Lys), four family members with novel mutation and their factor V activity and factor V antigen were all decreased about 50%. The Ser951LeufsTer8 is associated with decrease in the factor V level of the family, and it is the first mutation report in the position (Ser951LeufsTer8) with factor V deficiency.
Identifiants
pubmed: 33443922
doi: 10.1097/MBC.0000000000001003
pii: 00001721-202103000-00009
doi:
Substances chimiques
factor V clotting antigen
0
Factor V
9001-24-5
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
140-145Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Références
Thomassen MC, Castoldi E, Tans G, Magdeleyns EJ, Delaunoit C, Debusscher L, et al. Endogenous factor V synthesis in megakaryocytes contributes negligibly to the platelet factor V pool. Haematologica 2003; 88:1150–1156.
Ding Q, Shen W, Ye X, Wu Y, Wang H. Clinical and genetic features of protein C deficiency in 23 unrelated Chinese patients. Blood Cells Mol Dis 2013; 50:53–58.
Lippi G, Favaloro EJ, Montagnana M, Manzato F, Guidi GC, Franchini M. Inherited and acquired factor V deficiency. Blood Coagul Fibrinolysis 2011; 22:160–166.
Duckers C, Simioni P, Rosing J, Castoldi E. Advances in understanding the bleeding diathesis in factor V deficiency. Br J Haematol 2009; 146:17–26.
Nogami K, Shinozawa K, Ogiwara K, Matsumoto T, Amano K, Fukutake K, et al. Novel FV mutation (W1920R, FVNara) associated with serious deep vein thrombosis and more potent APC resistance relative to FVLeiden. Blood 2014; 123:2420–2428.
Tracy PB, Mann KG. Abnormal formation of the prothrombinase complex: factor V deficiency and related disorders. Hum Pathol 1987; 18:162–169.
Vos HL. An online database of mutations and polymorphisms in and around the coagulation factor V gene. J Thromb Haemost 2007; 5:185–188.
Asselta R, Peyvandi F. Factor V deficiency. Semin Thromb Hemost 2009; 35:382–389.
Steen M, Miteva M, Villoutreix BO, Yamazaki T, Dahlbäck B. Factor V New Brunswick: Ala221Val associated with FV deficiency reproduced in vitro and functionally characterized. Blood 2003; 102:1316–1322.
Delev D, Pavlova A, Heinz S, Blaise MC, Chandra T, Poetsch B, et al. Modelling and expression studies of two novel mutations causing factor V deficiency. Thromb Haemost 2008; 1009:766–772.
Cheng X, Wang M, Jiang M, Bhugul PA, Hao X, Yang L. A protein C and plasminogen compound heterozygous mutation and a compound heterozygote of protein C in two related Chinese families. Blood Coagul Fibrinolysis 2016; 27:838–844.
Adams TE, Hockin MF, Mann KG, Everse SJ. The crystal structure of activated protein C-inactivated bovine factor Va: implications for cofactor function. Proc Natl Acad Sci U S A 2004; 101:8918–8951.
Nuzzo F, Bulato C, Nielsen BI, Lee K, Wielders SJ, Simioni P, et al. Characterization of an apparently synonymous F5 mutation causing aberrant splicing and factor V deficiency. Haemophilia 2015; 21:241–248.
van Wijk R, Nieuwenhuis K, van den Berg M, Huizinga EG, van der Meijden BB, Kraaijenhagen RJ, et al. Five novel mutatiorm in the gene for human blood coagulation factor V associated with type I factor V deficiency. Blood 2001; 98:358–367.
Yang L, Jin Y, Yang T, Chen X, Zhu L, Wang M. Analysis of phenotypes and genetic mutations in two pedigrees affected with hereditary protein C deficiency. Chin J Med Genet 2017; 34:10–14.
Gandrille S, Greengard JS, Alhenc-Gelas M, Juhan-Vague I, Abgrall JF, Jude B, et al. Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. The French Network on the behalf of INSERM. Blood 1995; 86:219–224.
Le W, Yu JD, Lu L, Tao R, You B, Cai X, et al. Association of the R485K polymorphism of the factor V gene with poor response to activated protein C and increased risk of coronary artery disease in the Chinese population. Clin Genet 2000; 57:296–303.
Faisel F, Romppanen EL, Hiltunen M, Helisalmi S, Laasanen J, Punnonen K, et al. Susceptibility to preeclampsia in Finnish women is associated with R485K polymorphism in the factor V gene, not with Leiden mutation. Eur J Hum Genet 2004; 12:187–191.
Castoldi E, Simioni P, Kalafatis M, Lunghi B, Tormene D, Girelli D, et al. Combinations of 4 mutations (FV RS06Q, FV H1299R, FV Y1702C, PT 20210GA) affecting tho prothrombinase complex in a thrombophilic family. Blood 2000; 96:1443–1448.