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Hypoglycosylation is a common finding in antithrombin deficiency in the absence of a SERPINC1 gene defect

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dc.contributor.authorMorena Barrio, María Eugenia de la
dc.contributor.authorMartínez Martínez, Irene
dc.contributor.authorCos, Carmen de
dc.contributor.authorWypasek, Ewa
dc.contributor.authorRoldán, Vanessa
dc.contributor.authorUndas, Anetta
dc.contributor.authorSherpenzeel, Monique van
dc.contributor.authorLefeber, Dirk
dc.contributor.authorToderici, Mara
dc.contributor.authorSevivas, Teresa
dc.contributor.authorEspaña, Francisco
dc.contributor.authorJaeken, Jaak
dc.contributor.authorCorral, Javier
dc.contributor.authorVicente, Vicente
dc.contributor.departmentMedicina
dc.date.accessioned2024-02-09T13:08:16Z
dc.date.available2024-02-09T13:08:16Z
dc.date.issued2016
dc.description© 2016 International Society on Thrombosis and Haemostasis. This document is the Published version of a Published Work that appeared in final form in Journal of Thrombosis and Haemostasis. To access the final edited and published work see https://doi.org/10.1111/jth.13372
dc.description.abstractEssentials We investigated the molecular base of antithrombin deficiency in cases without SERPINC1 defects. 27% of cases presented hypoglycosylation, transient in 62% and not restricted to antithrombin. Variations in genes involved in N-glycosylation underline this phenotype. These results support a new form of thrombophilia. Click here to listen to Dr Huntington's perspective on thrombin inhibition by the serpins. Summary: Background Since the discovery of antithrombin deficiency, 50 years ago, few new thrombophilic defects have been identified, all with weaker risk of thrombosis than antithrombin deficiency. Objective To identify new thrombophilic mechanisms. Patients/methods We studied 30 patients with antithrombin deficiency but no defects in the gene encoding this key anticoagulant (SERPINC1). Results A high proportion of these patients (8/30: 27%) had increased hypoglycosylated forms of antithrombin. All N-glycoproteins tested in these patients (α1-antitrypsin, FXI and transferrin) had electrophoretic, HPLC and Q-TOF patterns indistinguishable from those of the congenital disorders of glycosylation (rare recessive multisystem disorders). However, all except one had no mental disability. Moreover, intermittent antithrombin deficiency and hypoglycosylation was recorded in five out of these eight patients, all associated with moderate alcohol intake. Genetic analysis, including whole exome sequencing, revealed mutations in different genes involved in the N-glycosylation pathway. Conclusions Our study provides substantial and novel mechanistic insights into two disease processes, with potential implications for diagnosis and clinical care. An aberrant N-glycosylation causing a recessive or transient antithrombin deficiency is a new form of thrombophilia. Our data suggest that congenital disorders of glycosylation are probably underestimated, especially in cases with thrombosis as the main or only clinical manifestation.es
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dc.format.extent12es
dc.identifier.citationJournal of Thrombosis and Haemostasis 2016 14: 1549–60.
dc.identifier.doihttps://doi.org/10.1111/jth.13372.
dc.identifier.issnPrint: 1538-7933
dc.identifier.issnElectronic: 1538-7836
dc.identifier.urihttp://hdl.handle.net/10201/139145
dc.languageenges
dc.publisherElsevier
dc.relationÁmbito internacional, This work was supported by PI12/00657, PI15/00079, RD12/0042/0050, RD12/0042/0029 and CB15/00055 from ISCIII (Instituto de Salud Carlos III), Fundaci on Espa~nola de Trombosis y Hemostasia and a GATRA Grifols Award. M. E. de la Morena-Barrio holds a post-doctoral contract from the Ministerio de Economia y Competitividad FPDI-2013-17273. I. Mart ınez-Mart ınez holds a ‘Miguel Servet’ contract from ISCIII.es
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectAntithrombin III deficiencyen
dc.subjectCongenital disorders of glycosylationen
dc.subjectGlycoproteinsen
dc.subjectThrombophiliaen
dc.subjectVenous thrombosisen
dc.titleHypoglycosylation is a common finding in antithrombin deficiency in the absence of a SERPINC1 gene defectes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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