A case of factor X (FX) deficiency due to novel mutation V196M, FX Hofu

Shinohara, Kenji; Adachi, Mayumi; Matsui, Kumiko; Matsuda, Kazuhiro; Nagaya, Satomi; Morishita, Eriko

doi:10.1007/s12185-008-0035-1

Cited by 6 publications

(9 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1), comprising 82 missense mutations (representing 78% of all mutations), 14 deletions (3 gross deletions þ 11 microdeletions), 6 splice site mutations, 2 nonsense mutations, and 1 mutation in the 5 0 flanking region, were reported in F10. 16,[29][30][31][32][33][34][35][36][37][38] Several polymorphisms were also identified, with no effect on FX levels. 25,39,40 Although most mutations are located in exon 8, the number of mutations located in each exon is proportional to the length of the exon itself, indicating the absence of a hot-spot region in F10.…”

Section: Genotype Analysismentioning

confidence: 99%

Factor X Deficiency

Menegatti¹,

Peyvandi²

2009

Semin Thromb Hemost

128

119

View full text Add to dashboard Cite

Factor X (FX) deficiency is a rare, recessively inherited bleeding disorder representing 10% of all rare bleeding diseases and affecting 1 in every 1,000,000 people. Its clinical presentation places FX deficiency among the most severe of the rare coagulation defects, typically including hemarthroses, hematomas, and umbilical cord, gastrointestinal, and central nervous system bleeding. Phenotype diagnosis is based on the concomitant prolongation of the prothrombin time and activated partial thromboplastin time. Through the measurement of plasma level of FX antigen and its coagulant activity, two main types of deficiency can be distinguished: type I (concomitantly low levels of activity and antigen) and type II (low coagulant activity, but normal or borderline antigen levels). FX protein is mainly synthesized by the liver and is encoded by a gene ( F10) of 27 kb located on chromosome 13, containing 8 exons. One hundred five mutations on F10 have been identified to date, 78% being missense mutations, with no hot-spot regions. There is no specific FX concentrate available, and current treatment includes the administration of fresh-frozen plasma or prothrombin complex concentrates (PCCs) containing FX in addition to other vitamin K-dependent factors. Administration of PCCs is associated with the risk of thromboembolic complication due to the unknown concentrations of other coagulant factors; however, to overcome this problem, a concentrate containing well-defined amounts of FX (and FIX) has recently been developed.

show abstract

Section: Genotype Analysismentioning

confidence: 99%

Factor X Deficiency

Menegatti¹,

Peyvandi²

2009

Semin Thromb Hemost

128

119

View full text Add to dashboard Cite

show abstract

“…Recombinant FX proteins carrying these six mutations were also produced in the present study, and how each mutant protein causes this disorder was examined. We previously reported a variant of FX carrying the amino acid substitution p.Val236Met as factor X Hofu in 2008 . Other mutations have also been reported.…”

Section: Discussionmentioning

confidence: 97%

“…FX activities in culture supernatants were determined using the prothrombin time. Samples prepared for measuring FX antigen levels were used for this assay …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Congenital coagulation factor X deficiency: Genetic analysis of five patients and functional characterization of mutant factor X proteins

et al. 2018

Self Cite

View full text Add to dashboard Cite

Congenital factor X (FX) deficiency is a rare bleeding disorder that is inherited as an autosomal recessive trait. In this study, a genetic analysis of the FX gene was performed in five families with this disorder. Four heterozygous mutations [p.Gly154Arg, p.Val236Met, p.Gly263Val and p.Arg387Cys] and one pair of compound heterozygous FX gene mutations consisting of p.Gly406Ser and p.Val424Phe were identified. Mutant FX proteins containing the identified amino acid substitutions were also expressed in cultured cells. These proteins were analysed by enzyme-linked immunosorbent assay and pulse-chase experiments. The results demonstrated normal intracellular synthesis and extracellular secretion of mutant FX proteins carrying the p.Val236Met, p.Arg387Cys and p.Gly406Ser amino acid substitutions. However, the results also showed that the p.Gly154Arg, p.Gly263Val and p.Val424Phe proteins were secreted less efficiently than the wild-type protein, although they were synthesized normally in the cell. Collectively, these observations suggest that the amino acid substitutions p.Gly154Arg, p.Gly263Val and p.Val424Phe induce protein misfolding, leading to the intracellular degradation of many FX proteins containing any of these mutations, and ultimately to the development of FX deficiency. On the other hand, for the p.Val236Met, p.Arg387Cys and p.Gly406Ser mutant proteins, we hypothesize that secreted FX proteins have impaired coagulant activities due to functional defects caused by these amino acid substitutions.

show abstract

“…To date, more than 130 mutations related to FX deficiency have been identified [14]. There are approximately 20 FX-deficient patients in Japan, and the causative mutation in 5 families has been reported [15][16][17][18][19]. Approximately, 75 % of patients with FX deficiency have missense mutations, and FX activity levels of most affected individuals are less than 1 % [14,20].…”

Section: Introductionmentioning

confidence: 99%

Factor X M402T: a homozygous missense mutation identified as the cause of cross-reacting material-reduced deficiency

et al. 2014

View full text Add to dashboard Cite

We investigated a mildly hemorrhagic patient with factor X (FX) deficiency to identify the nature of his defect by comprehensive analyses. A 42-year-old Japanese man was admitted to our hospital for uncontrolled gingival hemorrhage. His FX activity based on prothrombin time (PT) and activated partial thromboplastin time (aPTT) and FX antigen were <1, 6.5 and 11 %, respectively. A homozygous M402T missense mutation (c.1205 t>c; p.Met402Thr) was identified in the FX gene (F10) from both the patient and his brother. The mutation was not detected in the F10 of 82 unrelated normal Japanese individuals. We studied the functional consequences of this mutation by expressing mutant FX-M402T protein in HEK293 cells. This analysis revealed that the antigen of the FX-M402T mutants was approximately 26 % that of the wild-type FX in conditioned media. The FX-specific activity of FX-M402T mutants measured by a one-stage clotting assay based upon PT and aPTT, and a chromogenic assay using Russell's viper venom in the concentrated media was 7.7, 31.7, and 41.2 % of wild type, respectively. The results suggest that the mutation FX-M402T may cause a secretion defect and a molecular abnormality in FX.

show abstract

A case of factor X (FX) deficiency due to novel mutation V196M, FX Hofu

Cited by 6 publications

References 9 publications

Factor X Deficiency

Factor X Deficiency

Congenital coagulation factor X deficiency: Genetic analysis of five patients and functional characterization of mutant factor X proteins

Factor X M402T: a homozygous missense mutation identified as the cause of cross-reacting material-reduced deficiency

Contact Info

Product

Resources

About