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Título: Hypoglycosylation is a common finding in antithrombin deficiency in the absence of a SERPINC1 gene defect
Fecha de publicación: 2016
Editorial: Elsevier
Cita bibliográfica: Journal of Thrombosis and Haemostasis 2016; 14: 1549–60.
ISSN: Print: 1538-7933
Electronic: 1538-7836
Palabras clave: Antithrombin III deficiency
Congenital disorders of glycosylation
Glycoproteins
Thrombophilia
Venous thrombosis
Resumen: Essentials 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.
Autor/es principal/es: Morena Barrio, María Eugenia de la
Martínez Martínez, Irene
Cos, Carmen de
Wypasek, Ewa
Roldán, Vanessa
Undas, Anetta
Sherpenzeel, Monique van
Lefeber, Dirk
Toderici, Mara
Sevivas, Teresa
España, Francisco
Jaeken, Jaak
Corral, Javier
Vicente, Vicente
Facultad/Departamentos/Servicios: Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Medicina
URI: http://hdl.handle.net/10201/139145
DOI: https://doi.org/10.1111/jth.13372.
Tipo de documento: info:eu-repo/semantics/article
Número páginas / Extensión: 12
Derechos: info:eu-repo/semantics/embargoedAccess
Descripción: © 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
Aparece en las colecciones:Artículos: Medicina

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