Jessenius Faculty of Medicine in Martin, BioMed , Martin, Slovakia, 3Division of ... Yes, I would like to apply for a Young Investigators Award / Prix d'honneur de ...
Abstract Submission 2. Clotting ECTH-483 Two mutations in the FGB gene in patients with a quantitative fibrinogen disorder with bleeding and thrombotic phenotype Tomas Simurda* 1, Jana Zolkova1, Zuzana Snahnicanova2, Dusan Loderer2, Jan Hudecek1, Jan Stasko1, Ingrid Skornova1 , Zora Lasabova2, Alessandro Casini3, Rui Vilar4, Marguerite Neerman-Arbez4, Peter Kubisz1 1National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, 2Department of Molecular Biology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, BioMed , Martin, Slovakia, 3Division of Angiology and Haemostasis, University Hospitals of Geneva and Faculty of Medicine, Geneva, 4Department of Genetic Medicine and Development, University Medical School of Geneva, Geneva, Switzerland Please indicate your presentation preference: Poster Presentation Please indicate your type of research: Clinical and Applied Research I would like to apply for a Travel Grant: No Yes, I would like to apply for a Young Investigators Award / Prix d’honneur de la Jeunesse: Yes, I would like to apply for a Young Investigators Award and hereby confirm that I meet all the be Background: Congenital fibrinogen disorders are caused by mutations in the homozygous or compound heterozygous state in one of the three fibrinogen genes that affect the synthesis, assembly, intracellular processing, stability or secretion of fibrinogen. Patients can have bleeding manifestations or thrombotic complications and they can be also asymptomatic. Homozygous or heterozygous mutations in the three fibrinogen genes (Aα, Bβ, and γ) can lead to congenital quantitative fibrinogen disorders. Functional studies of mutant Bβ-chains revealed the importance of individual residues as well as three-dimensional structures for fibrinogen assembly and secretion. Aims: This study describes two homozygous fibrinogen Bβ chain mutations in two Slovak families with afibrinogenemia and hypofibrinogenemia. Methods: To identify the causative mutation peripheral blood samples were collected from all subjects. The coagulation-related tests and rotational thromboelastometry were performed. All exons and exon-intron boundaries of the fibrinogen genes (FGA, FGB and FGG) were amplified by PCR followed by direct sequencing. Results: A Bβ chain truncation (BβGln180Stop) was detected in a 28-year-old afibrinogenemic man with bleeding episodes including repeated haemorrhaging into muscles, joints, and soft tissues, and mucocutaneous bleeding and a Bβ missense mutation (BβTyr368His) was found in a 62-year-old hypofibrinogenemic man with recurrent deep and superficial venous thromboses of the lower extremities. The missense mutation was confirmed by molecular modelling. Summary/Conclusion: Studying the molecular anomalies and the modeling of fibrinogen mutants helps to understand the extremely complex machinery of fibrinogen biosynthesis and finally to better assess the correlation with the patients’ clinical course.
