The mutations are mainly missense mutations with nonsense and Frameshift mutations each occurring in 12.5% of cases. The causes of two fibrinogen abnormalities that characterize hypodysfibrinogenemia, i.e. circulation at reduced levels of fibrinogen at least some of which is dysfunctional, reflect different molecular mechanisms:
A heterozygous mutation in one of the two copies of either the FGA, FGB, or FGG gene leads to production of a fibrinogen that is both dysfunctional and poorly secreted into the blood stream, e.g. fibrinogen Vlissingen, fibrinogen Philadelphia, and fibrinogen Freiburg. A homozygous mutation in both copies of one of the cited genes leads to production of a fibrinogen that is both dysfunctional and poorly secreted into the blood stream, e.g. fibrinogen Otago,  fibrinogen Marburg, and fibrinogen Sfax. Two different mutations (see Compound heterozygosity) occur in each of the two copies of one of the cited genes, with one mutation coding for reduced formation of a functionally normal circulating fibrinogen and the second mutation coding for the circulation of a dysfunctional fibrinogen, e.g. fibrinogen Leipzig. Two different mutations occur in one copy of the cited genes, with one mutation causing hypofibrinogenemia and the other mutation coding for a dysfunctional fibrinogen, e.g. fibrinogen Keokuk.The following Table adds further information on the just cited examples of hypodysfibrinogenemias. The Table gives: a) each mutated proteins trivial name; b) the gene mutated (i.e. FGA, FGB, or FGG), its mutation site (i.e. numbered nucleotide in the cloned gene), and name of the nucleotides (i.e.
Bleeding is more frequent and severe in women of child-bearing age; these women may suffer miscarriages, menometrorrhagia, and excessive bleeding during child birth and/or the postpartum period. Excessive bleeding following major or minor surgery, including dental extractions, occurs in both females and males with the disorder. Thrombotic complications of the disorder are often (~50%) recurrent and can involve central and peripheral arteries, deep and superficial veins. Thrombotic events may be serious and involve occlusion of a cerebral artery leading to stroke, splanchnic venous thrombosis, and pulmonary thrombosis presumptively secondary to deep vein thrombosis. Fibrinogen
Circulating fibrinogen is a glycoprotein made of two trimers each of which is composed of three polypeptide chains, Aα (also termed α) encoded by the FGA gene, Bβ (also termed β) encoded by the FGB gene, and γ encoded by the FGG gene. All three genes are located on the long or "q" arm of human chromosome 4 (at positions 4q31.3, 4q31.3, and 4q32.1, respectively) and are the sites where mutations occur that code for a dysfunctional fibrinogen and/or reduced fibrinogen levels which are the cause of congenital hypodysfibrinogenemia. Pathophysiology
Congenital hypodysfibrinogenemia is inherited as an autosomal dominant disorder caused by at least 32 different types of single mutations. Ten of these mutations are in the fibrinogen alpha chain gene (also termed the FGA gene), 5 in the fibrinogen beta chain gene (also termed the FGB gene), and 17 in the fibrinogen gamma chain gene (also termed the FGG gen).