relation: http://publicatio.bibl.u-szeged.hu/29891/
title: Clinical and Molecular Characterization of Nine Novel Antithrombin Mutations
creator:  Kállai Judit
creator:  Gindele Réka
creator:  Pénzes-Daku Krisztina
creator:  Balogh Gábor
creator:  Bogáti Réka
creator:  Bécsi Bálint
creator:  Katona Éva
creator:  Oláh Zsolt
creator:  Ilonczai Péter
creator:  Boda Zoltán
creator:  Róna-Tas Ágnes
creator:  Nemes László
creator:  Marton Imelda
creator:  Bereczky Zsuzsanna
subject: 03.02. Klinikai orvostan
description: Antithrombin (AT) is the major plasma inhibitor of thrombin (FIIa) and activated factor X (FXa), and antithrombin deficiency (ATD) is one of the most severe thrombophilic disorders. In this study, we identified nine novel AT mutations and investigated their genotype-phenotype correlations. Clinical and laboratory data from patients were collected, and the nine mutant AT proteins (p.Arg14Lys, p.Cys32Tyr, p.Arg78Gly, p.Met121Arg, p.Leu245Pro, p.Leu270Argfs*14, p.Asn450Ile, p.Gly456delins_Ala_Thr and p.Pro461Thr) were expressed in HEK293 cells; then, Western blotting, N-Glycosidase F digestion, and ELISA were used to detect wild-type and mutant AT. RT-qPCR was performed to determine the expression of AT mRNA from the transfected cells. Functional studies (AT activity in the presence and in the absence of heparin and heparin-binding studies with the surface plasmon resonance method) were carried out. Mutations were also investigated by in silico methods. Type I ATD caused by altered protein synthesis (p.Cys32Tyr, p.Leu270Argfs*14, p.Asn450Ile) or secretion disorder (p.Met121Arg, p.Leu245Pro, p.Gly456delins_Ala_Thr) was proved in six mutants, while type II heparin-binding-site ATD (p.Arg78Gly) and pleiotropic-effect ATD (p.Pro461Thr) were suggested in two mutants. Finally, the pathogenic role of p.Arg14Lys was equivocal. We provided evidence to understand the pathogenic nature of novel SERPINC1 mutations through in vitro expression studies.
date: 2024
type: Folyóiratcikk
type: PeerReviewed
format: text
identifier: http://publicatio.bibl.u-szeged.hu/29891/1/Kallai.pdf
identifier:     Kállai Judit;  Gindele Réka;  Pénzes-Daku Krisztina;  Balogh Gábor;  Bogáti Réka;  Bécsi Bálint;  Katona Éva;  Oláh Zsolt;  Ilonczai Péter;  Boda Zoltán;  Róna-Tas Ágnes;  Nemes László;  Marton Imelda;  Bereczky Zsuzsanna: Clinical and Molecular Characterization of Nine Novel Antithrombin Mutations.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25 (5).   ISSN 1661-6596 (2024)     
identifier: doi:10.3390/ijms25052893
relation: https://doi.org/10.3390/ijms25052893
relation: 34742646
language: eng