A novel homozygous mutation (Gly1715Ser) causing hereditary factor V deficiency in a Chinese patient.
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:
Jan 2020
Jan 2020
Historique:
pubmed:
4
12
2019
medline:
4
6
2020
entrez:
3
12
2019
Statut:
ppublish
Résumé
: To explore the phenotype and genotype of a Chinese family with hereditary factor V deficiency. Routine blood coagulation indexes were detected by one-stage clotting method, whereas factor V antigen was detected by ELISA. All exons and intron-exon boundaries of F5 gene were amplified by PCR and sequenced directly. The suspected mutation was confirmed by reverse sequencing. Bioinformatics softwares were used to analyze the possible impact of this mutation. Phenotypic analysis showed that the proband had significantly prolonged prothrombin time and activated partial thromboplastin time, and his factor V clotting activity was decreased to 3%. Genetic analysis revealed a homozygous missense mutation c.5227G>A (p.Gly1715Ser) in exon 16 of F5 gene. Bioinformatics and structural analysis demonstrated this mutation was deleterious and could affect the integrity of local intermolecular structures. The missense mutation (Gly1715Ser) was responsible for the decrease of factor V clotting activity and factor V antigen in this family, and caused type I hereditary factor V deficiency.
Identifiants
pubmed: 31789663
doi: 10.1097/MBC.0000000000000871
pii: 00001721-202001000-00011
doi:
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
71-76Références
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.
Rosing J, Tans G. Coagulation factor V: an old star shines again. Thromb Haemost 1997; 78:427–433.
Yamazaki T, Nicolaes GA, Sørensen KW, Dahlbäck B. Molecular basis of quantitative factor V deficiency associated with factor V R2 haplotype. Blood 2002; 100:2515–2521.
Dahlbäck B. Procoagulant and anticoagulant properties of coagulation factor V: factor V Leiden (APC resistance) causes hypercoagulability by dual mechanisms. J Lab Clin Med 1999; 133:415–422.
Wang X, Tang N, Lu Y, Li D. Congenital factor V deficiency and decreased VWF in a Chinese male patient with hematuria. Haemophilia 2018; 24:e16–e18.
Dorgalaleh A, Alavi SE, Tabibian S, Soori S, Moradi E, Bamedi T, et al. Diagnosis, clinical manifestations and management of rare bleeding disorders in Iran. Hematology 2017; 22:224–230.
Thalji N, Camire RM. Parahemophilia: new insights into factor V deficiency. Semin Thromb Hemost 2013; 39:607–612.
Wang Y, Zhu L, Ye L, Xie Y, Pan J, Wang M. Factor V deficiency caused by a novel nonsense mutation (Gln2031stop) in a Chinese patient. Blood Coagul Fibrinolysis 2014; 25:283–285.
Campello E, Spiezia L, Simioni P. Diagnosis and management of factor V Leiden. Expert Rev Hematol 2016; 9:1139–1149.
Prüller F, Raggam RB, Mangge H, Truschnig-Wilders M, Matzhold EM, Weiss EC, et al. A novel factor V mutation causes a normal activated protein C ratio despite the presence of a heterozygous F5 R506Q (factor V Leiden) mutation. Br J Haematol 2013; 163:414–417.
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.
Jenny RJ, Pittman DD, Toole JJ, Kriz RW, Aldape RA, Hewick RM, et al. Complete cDNA and derived amino acid sequence of human factor V. Proc Natl Acad Sci U S A 1987; 84:4846–4850.
Foster WB, Nesheim ME, Mann KG. The factor Xa-catalyzed activation of factor V. J Biol Chem 1983; 258:13970–13977.
Suzuki K, Dahlback B, Stenflo J. Thrombin-catalyzed activation of human coagulation factor V. J Biol Chem 1982; 257:6556–6564.
Delev D, Pavlova A, Heinz S, Seifried E, Oldenburg J. Factor 5 mutation profile in German patients with homozygous and heterozygous factor V deficiency. Haemophilia 2009; 15:1143–1153.
Castoldi E, Simioni P, Kalafatis M, Lunghi B, Tormene D, Girelli D, et al. Combinations of 4 mutations (FV R506Q, FV H1299R, FV Y1702C, PT 20210G/A) affecting the prothrombinase complex in a thrombophilic family. Blood 2000; 96:1443–1448.
Yamakage N, Ikejiri M, Okumura K, Takagi A, Murate T, Matushita T, et al. A case of coagulation factor V deficiency caused by compound heterozygous mutations in the factor V gene. Haemophilia 2006; 12:172–178.