Comparison of clinical phenotype with genetic and laboratory results in 31 patients with congenital dysfibrinogenemia in northern Slovakia
- 12 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in International Journal of Hematology
- Vol. 111 (6), 795-802
- https://doi.org/10.1007/s12185-020-02842-9
Abstract
Congenital dysfibrinogenemia (CD) is a rare disorder of hemostasis. The majority of cases are caused by heterozygous missense mutations in one of the three fibrinogen genes. Patients with CD may experience bleeding and thrombosis, but many are asymptomatic. To better describe the clinical, laboratory, and genotypic picture of CD, we evaluated 31 patients from seven unrelated families using standard coagulation tests and genetic analysis. The clinical phenotype consisted of bleeding in 13/31 (42%) patients; other patients (18/31; 58%) were asymptomatic. Among patients with bleeding, symptoms were mostly in single anatomical sites, with variable intensity of bleeding. Compared to results from a previous large systematic survey, our results showed a similar mean bleeding score, but a higher incidence of bleeding episodes without thrombotic complications. In the present study, we identified three known pathogenic point mutations in the FGA (c.95G > A, c.104G > A) and FGB (c.586C > T) genes. The variants of CD identified in this cross-sectional study were either asymptomatic or had bleeding manifestations and showed similar laboratory features, irrespective of genotype. Results from genetic and clinical studies will continue to yield valuable information on the structure and function of the fibrinogen molecule.Keywords
This publication has 44 references indexed in Scilit:
- Congenital Fibrinogen Disorders: An UpdateSeminars in Thrombosis and Hemostasis, 2013
- Mechanisms of fibrin polymerization and clinical implicationsBlood, 2013
- ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disordersJournal of Thrombosis and Haemostasis, 2010
- Inherited dysfibrinogenemia: clinical phenotypes associated with five different fibrinogen structure defectsBlood Coagulation & Fibrinolysis, 2010
- Treatment of patients with dysfibrinogenemia and a history of abortions during pregnancyBlood Coagulation & Fibrinolysis, 2009
- Molecular characterization of the first missense mutation in the fibrinogen Aalpha-chain gene identified in a compound heterozygous afibrinogenemic patientBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2007
- Inherited abnormalities of fibrinogen: 10-year clinical experience of an Italian groupBlood Coagulation & Fibrinolysis, 2006
- Fibrinogen Saint-Germain I: a case of the heterozygous Aα GLY 12 → VAL fibrinogen variantBlood Coagulation & Fibrinolysis, 2002
- Fibrinogen Detroit—a Molecular Defect in the N-terminal Disulphide Knot of Human Fibrinogen?Nature, 1968