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Semin Thromb Hemost 2016; 42(04): 356-365
DOI: 10.1055/s-0036-1571340
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders

Marguerite Neerman-Arbez
1   Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland
,
Philippe de Moerloose
2   Division of Angiology and Haemostasis, Faculty of Medicine, University Hospitals of Geneva, Geneva, Switzerland
,
Alessandro Casini
2   Division of Angiology and Haemostasis, Faculty of Medicine, University Hospitals of Geneva, Geneva, Switzerland
› Author Affiliations
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Publication History

Publication Date:
28 March 2016 (online)

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Abstract

Congenital fibrinogen disorders are classified into two types of plasma fibrinogen defects: type I (quantitative fibrinogen deficiencies), that is, hypofibrinogenemia or afibrinogenemia, in which there are low or absent plasma fibrinogen antigen levels, respectively, and type II (qualitative fibrinogen deficiencies), that is, dysfibrinogenemia or hypodysfibrinogenemia, in which there are normal or reduced antigen levels associated with disproportionately low functional activity. These disorders are caused by mutations in the three fibrinogen-encoding genes FGA, FGB, and FGG. Afibrinogenemia is associated with mild to severe bleeding, whereas hypofibrinogenemia is often asymptomatic. For these quantitative disorders, the majority of mutations prevent protein production. However, in some cases, missense or late-truncating nonsense mutations allow synthesis of the mutant fibrinogen chain, but intracellular fibrinogen assembly and/or secretion are impaired. Qualitative fibrinogen disorders are associated with bleeding, thrombosis, or both thrombosis and bleeding, but many dysfibrinogenemias are asymptomatic. The majority of cases are caused by heterozygous missense mutations. Here, we review the laboratory and genetic diagnosis of fibrinogen gene anomalies with an updated discussion of causative mutations identified.

Keywords

congenital fibrinogen disorders - mutations - afibrinogenemia - hypofibrinogenemia - dysfibrinogenemia - hypodysfibrinogenemia - bleeding - thrombosis
 

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