Fibrinogen Martin: Scientists from Comenius University identify a previously unknown mutation of congenital fibrinogen disorder
Congenital fibrinogen disorders are rare disorders of coagulation. Tomáš Šimurda, a doctoral student at Comenius University’s Jessenius Faculty of Medicine in Martin, and a team of researchers have described a hitherto unknown mutation of this disease which has been given the name Fibrinogen Martin.
Rare congenital haemophilic disorders of haemostasis are a group of diseases where there is a lowered or a complete lack of plasma proteins (coagulation factors), which are essential in the coagulation process. Congenital fibrinogen disorders are rare disorders of coagulation concerning plasma proteins, which during the formation of fibrous fibrin help close the damaged vascular wall in the place of injury along with blood platelets. These disorders can be classified as quantitative (afibrinogenemia and hypofibrinogenemia) or qualitative (dysfibrinogenemia).
Research into this type of disease has been undertaken by Tomáš Šimurda, a doctoral student at the Jessenius Faculty of Medicine in Martin alongside fellow doctoral students Dušan Loderer and Zuzana Sňahničanová under the guidance of Professor Peter Kubisz, Professor Ján Staško, Dr Juraj Sokol, and Associate Professor Zora Lasabová.
“Since the first description of congenital afibrinogenemia in 1920 and hypofibrinogenemia in 1935, there have been over 200 registered cases of quantitative fibrinogen disorders. There have been more occurrences of qualitative abnormalities, which have been known about since the 1960s, with more than 400 cases of dysfibrinogenemia having been described to date,” said Šimurda.
“The estimated occurrence of afibrinogenemia in the world is around one case in one million people. Hypofibrinogenemia and dysfibrinogenemia are a lot more common, but their exact number is hard to ascertain as there is a large number of asymptomatic cases. In Slovakia the occurrence of afibrinogenemia is one case in five million people, with there being one case of a severe form of hypofibrinogenemia for every 100,000 people and one case of a severe form of dysfibrinogenemia for every 40,000 people. With the gradual development of sophisticated methods of analysis, the definition and classification of fibrinogen abnormalities has changed. Clinical occurrences are highly variable, and in cases of severe bleeding they can be paradoxically associated with thrombosis,” the young researcher added.
In recent years, the function of separate parts of the complex molecule of fibrinogen has been defined and the genetic foundations of fibrinogen disorders have been revealed. At the Department of Hematology and Transfusiology at the Jessenius Faculty of Medicine and the University Hospital in Martin, where the National Hemostatis and Thrombosis Centre is located, the research team and the Institute of Molecular Biology at the Jessenius Faculty of Medicine have managed to identify a previously unknown mutation in the beta chain of the FGB gene which encodes the fibrinogen molecule in the only patient in Slovakia who suffers from the severe blood disorder of congenital afibrinogenemia.
“Given that this mutation was discovered at our faculty, it was given the name ‘Fibrinogen Martin’. Since 2016 we have managed to diagnose 58 patients with rare congenital fibrinogen disorders (hypofibrinogenemia and dysfibrinogenemia) where we have supplemented standard diagnostics with global tests of hemostasis (a test of the generation of thrombin, rotational thromboelastography), which are important in terms of correctly managing treatment. In the near future, we will undertake a genetic analysis on all of these patients using new sequencing methods,” Šimurda said.
The Martin-based researchers are currently intensively working on the connection between the clinical phenotypes and types of genetic disorders as well as on the possibilities of predicting the clinical progression of disease upon the basis of a specific molecular defect. Knowledge of the molecular mechanism is an essential requirement for the development of genetic therapy.
“I am glad that these talented doctoral students are using their creativity and the opportunities provided to them by our research centres. The discovery of a new mutation of the congenital fibrinogen disorder which has been given the unique name of ‘Martin’ is a successful example of this. This work contributes to the development of diagnostics in this area and ultimately to the development of genetic therapy for the effective treatment of patients with this congenital disorder both in Slovakia and abroad,” said the Comenius University Rector, Professor Karol Mičieta.