Skip to Main content Skip to Navigation
Journal articles

A rare coding mutation in the MAST2 gene causes venous thrombosis in a French family with unexplained thrombophilia: The Breizh MAST2 Arg89Gln variant

Abstract : Rare variants outside the classical coagulation cascade might cause inherited thrombosis. We aimed to identify the variant(s) causing venous thromboembolism (VTE) in a family with multiple relatives affected with unprovoked VTE and no thrombophilia defects. We identified by whole exome sequencing an extremely rare Arg to Gln variant (Arg89Gln) in the Microtubule Associated Serine/Threonine Kinase 2 (MAST2) gene that segregates with VTE in the family. Free-tissue factor pathway inhibitor (f-TFPI) plasma levels were significantly decreased in affected family members compared to healthy relatives. Conversely, plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in affected members than in healthy relatives. RNA sequencing analysis of RNA interference experimental data conducted in endothelial cells revealed that, of the 13,387 detected expressed genes, 2,354 have their level of expression modified by MAST2 knockdown, including SERPINE1 coding for PAI-1 and TFPI. In HEK293 cells overexpressing the MAST2 Gln89 variant, TFPI and SERPINE1 promoter activities were respectively lower and higher than in cells overexpressing the MAST2 wild type. This study identifies a novel thrombophilia-causing Arg89Gln variant in the MAST2 gene that is here proposed as a new molecular player in the etiology of VTE by interfering with hemostatic balance of endothelial cells.
Document type :
Journal articles
Complete list of metadata

https://hal.sorbonne-universite.fr/hal-03145009
Contributor : Hal Sorbonne Université Gestionnaire <>
Submitted on : Thursday, February 18, 2021 - 9:08:44 AM
Last modification on : Tuesday, March 23, 2021 - 4:05:03 PM

File

journal.pgen.1009284.pdf
Publication funded by an institution

Identifiers

Citation

Lenaick Gourhant, Omar Soukarieh, David-Alexandre Trégouët, Pierre-Emmanuel Morange, Franck Peiretti, et al.. A rare coding mutation in the MAST2 gene causes venous thrombosis in a French family with unexplained thrombophilia: The Breizh MAST2 Arg89Gln variant. PLoS Genetics, Public Library of Science, 2021, 17 (1), pp.e1009284. ⟨10.1371/journal.pgen.1009284⟩. ⟨hal-03145009⟩

Share

Metrics

Record views

144

Files downloads

48