ArticleJournal of thrombosis and haemostasis : JTH2011
Most factor VIII B domain missense mutations are unlikely to be causative mutations for severe hemophilia A: implications for genotyping.
Article in Journal of thrombosis and haemostasis : JTH, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 32 citations in OpenAlex.
- Review
- A scan of pleiotropic immune mediated disease genes identifies novel determinants of baseline FVIII inhibitor status in hemophilia A.Genes and immunity · 2025Article
- Ancient origin of the furin sequence in the wolf F8 gene.Open veterinary journal · 2025Article
- Advances in biopharmaceutical products for hemophilia.iScience · 2024Review
- Mutational Profile in Romanian Patients with Hemophilia A.International journal of molecular sciences · 2024Article
- Translational readthrough atHaematologica · 2023Article
- Variant spectrum ofFrontiers in genetics · 2023Article
- Analysis of 363 Genetic Variants in F5 via an Interactive Web Database Reveals New Insights into FV Deficiency and FV Leiden.TH open : companion journal to thrombosis and haemostasis · 2023Article
- The Possible Non-Mutational Causes of FVIII Deficiency: Non-Coding RNAs and Acquired Hemophilia A.Frontiers in medicine · 2021Review
- Mutation analysis in the F8 gene in 485 families with haemophilia A and prenatal diagnosis in China.Haemophilia : the official journal of the World Federation of Hemophilia · 2021Article
- In Silico Study of Correlation between Missense Variations ofTurkish journal of haematology : official journal of Turkish Society of Haematology · 2020Article
- Further Evidence That MicroRNAs Can Play a Role in Hemophilia A Disease Manifestation:Frontiers in cell and developmental biology · 2020Article
- Constitutive and Inducible Systems for Genetic In Vivo Modification of Mouse Hepatocytes Using Hydrodynamic Tail Vein Injection.Journal of visualized experiments : JoVE · 2018Article
- Mutational Profiles ofMediterranean journal of hematology and infectious diseases · 2018Article
- [Analysis of factor Ⅷ gene mutations in a family with hemophilia A].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2016Article
- Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype.Blood · 2013Article
- The CDC Hemophilia A Mutation Project (CHAMP) mutation list: a new online resource.Human mutation · 2013Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledBACKGROUND &
objectiveThe factor VIII (FVIII) B domain shares very little amino acid homology with other known proteins and is not directly necessary for procoagulant activity. Despite this, missense mutations within the B domain have been reported in patients with hemophilia A. Given that the B domain is dispensable for secretion and function of FVIII, we hypothesized that these mutations should not be causative of hemophilia A in these patients.
methodsPlasmid vectors containing B domain missense mutations that were reported to be associated with moderate/severe hemophilia A (T751S, D826E, V993L, H1047Y, T1353A, N1441K, L1462P, E1579D, A1591S, P1641L and S1669L) were analyzed for their effect on synthesis and secretion compared with FVIII wild-type (WT) following transient transfection into COS-1 and CHO cells in vitro. Further, H1047Y, N1441K and E1579D mutants were expressed in vivo in a hemophilia A mouse model by hydrodynamic tail-vein injection.
resultsFVIII activity and antigen levels for all mutants expressed into the conditioned media of COS-1 and CHO cells were similar to FVIII WT. Also, plasma expression of these mutants was similar to FVIII WT in hemophilia A mice. An in vivo tail clip bleeding assay also demonstrated that blood loss from hemophilia A mice expressing FVIII WT, H1047Y, N1441K and E1579D was similar.
conclusionsWe conclude that most missense mutations within the FVIII B domain would be unlikely to lead to severe hemophilia A and that the majority of such missense mutations represent polymorphisms or non-pathologic mutations.
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