bleeding manifestations varying from mild to severe.
fibrinogen is a hexamer composed of two sets of three polypeptides (Aalpha, Bbeta, and gamma). Each polypeptide is encoded by a distinct gene, FGA, FGB, and FGG, all three clustered in a region of 50 kb on 4q31
common recurrent mutation at the donor splice site of FGA intron 4 (IVS4+1G>T)
86p.100 of afibrinogenemia alleles analyzed to date have truncating mutations of FGA
in FGA, FGB or FGG genes
. hereditary fibrinogen disorders include type I deficiencies (afibrinogenemia and hypofibrinogenemia, i.e. quantitative defects), with low or unmeasurable levels of immunoreactive protein; and type II deficiencies (dysfibrinogenemia and hypodysfibrinogenemia, i.e. qualitative defects), showing normal or altered antigen levels associated with reduced coagulant activity
a deep intronic mutation creates a consensus exonic splicing enhancer motif that results in afibrinogenemia caused by aberrant mRNA splicing, which can be corrected in vitro with antisense oligonucleotide treatment (Davis 2009)