Phenotype and genotype analysis of hereditary hypofibrinogenaemia and dysfibrinogenaemia

Česká verzia

Authors: A. Bátorová ¹; D. Horváthová ¹; P. De Moerloose ²; M. Neerman-Arbez ³; M. Mistrík ¹
Authors place of work: Národné hemofilické centrum Kliniky hematológie a transfuziológie LF UK, Bratislava, Slovenská republika, prednosta doc. MUDr. Martin Mistrík, Ph. D. ¹; Division of Angiology and Hemostasis, University Hospital, Ženeva, Švajčiarsko, director prof. Dr. H. Bounameaux ²; Departement of Genetic Medicine and Development, University Medical School, Ženeva, Švajčiarsko, director prof. Dr. Stylianos Antonarakis ³
Published in the journal: Vnitř Lék 2005; 91(7 a 8): 802-808
Category: 128th Internal Medicine Day - 21rd Vanysek's Day Brno 2005

Summary

Inherited fibrinogen disorders, either quantitative (afibrinogenemia, hypofibrinogenemia) or qualitative (dysfibrinogenemia) represent a rare blood coagulation disorders. Clinical manifestation is variable and the bleeding may paradoxically be associated with the thrombotic events. Recently the function of all components of the complex fibrinogen molecule as well as the molecular basis of fibrinogen disorders were defined. Currently the attention is focused upon the relationship between the clinical phenotype and the type of molecular defect with the aim to predict the clinical picture of disease. The phenotype analysis in 67 patients with inherited hypofibrinogenemia and dysfibrinogenemia registered in the National Registry of Inherited Bleeding Disorders in Bratislava has confirmed a wide variation in bleeding manifestation and unpredictable association of bleeding with the invasive procedures in patients with fibrinogen disorders. Genetic analysis in 24 patients has revealed three heterozygous novel mutations: in hypofibrinogenemia the exon 1 FGG gene mutation (Trp3→Stop) and exon 7 FGG gene mutations (Trp253→Cys), in dysfibrinogenemia the exon 2 FGA gene mutation (Aα Gly13→Glu). The results of our study, although limited, suggest an importance of the mutation identification in patients with inherited disorders of fibrinogen. However, further studies are needed to improve the predictive value of the mutational type for the clinical phenotype in particular patient.

Key words:
hypofibrinogenemia – dysfibrinogenemia – bleeding – thrombosis – gene mutations

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