dc.date.accessioned | 2022-03-18T17:59:05Z | |
dc.date.available | 2022-03-18T17:59:05Z | |
dc.date.created | 2022-02-13T11:50:00Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Andersen, Elisabeth Dugarte, Maria Eugenia Chollet Bernardi, Francesco Branchini, Alessio Baroni, Marcello Mariani, Guglielmo Dolce, Alberto Batorova, Angelika Skarpen, Ellen Myklebust, Christiane Filion Skretting, Grethe Sandset, Per Morten . The factor vii variant p.A354v-p.p464hfs: Clinical versus intracellular and biochemical phenotypes induced by chemical chaperones. Applied Sciences. 2021, 11(13) | |
dc.identifier.uri | http://hdl.handle.net/10852/92595 | |
dc.description.abstract | (1) Background: Congenital factor (F) VII deficiency is caused by mutations in the F7 gene. Patients with modest differences in FVII levels may display large differences in clinical severity. The variant p.A354V-p.P464Hfs is associated with reduced FVII antigen and activity. The aim of the study was to investigate the clinical manifestation of this variant and the underlying molecular mechanisms. (2) Methods: Analyses were conducted in 37 homozygous patients. The recombinant variant was produced in mammalian cells. (3) Results: We report a large variation in clinical phenotypes, which points out genetic and acquired components beyond F7 mutations as a source of variability. In contrast, patients displayed similarly reduced FVII plasma levels with antigen higher than its activity. Comparative analysis of the recombinant variant and of plasma samples from a subset of patients indicated the presence of an elongated variant with indistinguishable migration. Treatment of cells with the chemical chaperone 4-phenylbutyrate (4-PBA) improved the intracellular trafficking of the variant and increased its secretion to the conditioned medium up to 2-fold. However, the effect of 4-PBA on biological activity was marginal. (4) Conclusions: Chemical chaperones can be used as biochemical tools to study the intracellular fate of a trafficking-defective FVII variant. | |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | The factor vii variant p.A354v-p.p464hfs: Clinical versus intracellular and biochemical phenotypes induced by chemical chaperones | |
dc.type | Journal article | |
dc.creator.author | Andersen, Elisabeth | |
dc.creator.author | Dugarte, Maria Eugenia Chollet | |
dc.creator.author | Bernardi, Francesco | |
dc.creator.author | Branchini, Alessio | |
dc.creator.author | Baroni, Marcello | |
dc.creator.author | Mariani, Guglielmo | |
dc.creator.author | Dolce, Alberto | |
dc.creator.author | Batorova, Angelika | |
dc.creator.author | Skarpen, Ellen | |
dc.creator.author | Myklebust, Christiane Filion | |
dc.creator.author | Skretting, Grethe | |
dc.creator.author | Sandset, Per Morten | |
cristin.unitcode | 185,53,49,11 | |
cristin.unitname | Avdeling for blodsykdommer | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 2000895 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Applied Sciences&rft.volume=11&rft.spage=&rft.date=2021 | |
dc.identifier.jtitle | Applied Sciences | |
dc.identifier.volume | 11 | |
dc.identifier.issue | 13 | |
dc.identifier.pagecount | 0 | |
dc.identifier.doi | https://doi.org/10.3390/app11135762 | |
dc.identifier.urn | URN:NBN:no-95173 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2076-3417 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/92595/1/The%2Bfactor%2Bvii%2Bvariant%2Bp.A354v-p.p464hfs%2BClinical%2Bversus%2Bintracellular%2Band%2Bbiochemical%2Bphenotypes%2Binduced%2Bby%2Bchemical%2Bchaperones.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 5762 | |