Congenital afibrinogenemia (Congenital Afibrinogenemia) - Genes FGA, FGB, FGG
Afibrinogenemia is a hemorrágic or caused by impaired blood clotting process. Normally, blood coagulation protects the body from injury by closing the damaged blood vessels and prevent blood loss. However, in people with afibrinogenaemia bleeding can not be controlled. Often, l os newborns with this condition prolonged bleeding from the umbilical cord after birth. There are also frequent nosebleeds (epistaxis) and bleeding of the gums or tongue after a minor trauma or even in the absence of previous injury. Some affected individuals have joint bleeding (hemarthrosis) or muscles (hematoma). Rarely, bleeding occurs in the brain or other internal organs, which can be fatal. In addition, as women afibrinogenaemia l may have menorrhagia. Without proper treatment, the affected women may have difficulty carrying a pregnancy to term and have miscarriages.
This process is due to mutations in one of the three genes, FGA, FGB, FGG or. located on the long arm of chromosome 4 (4q28). Each of these genes encodes a subunit of the protein fibrinogen. The FGA gene encodes the alpha chain (Aa), the FGB gene encoding the beta chain (B.beta) and FGG gene encodes gamma chain (G?). Two complete sets of the three chains combine to form functional fibrinogen. Fibrinogen is important for coagulation, and in response to injury, fibrinogen is converted to fibrin, which is the major component of blood clots. Fibrin forms a stable network forming the blood clot.
Most of the identified mutations FGA, FGB and FGG genes in people with afibrinogenemia introduce a premature stop signal in the gene expression to form each of the proteins, respectively. If any of the three synthesized proteins affected, it is not functional. When any subunit is not normal, or is absent, it can not constitute fibrinogen, which results in an absence of fibrin. Consequently, blood clots are not formed after injury. Alterations in the synthesis of fibrinogen due to mutations of the genes encoding each of its components, causing hypofibrinogenemia, dysfibrinogenemia, or hypodysfibrinogenemia. Hypofibrinogenemia characterized by decreasing fibrinogen levels in blood. Dysfibrinogenemia is characterized by abnormal functioning of fibrinogen, although the protein is present in normal é concentrations. The hypodysfibrinogenemia is characterized by low concentration and abnormal functioning of existing blood fibrinogen.
Afibrinogenemia is inherited as an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with congenital afibrinogenemia, by complete PCR amplification of the exons of the FGA, FGB and FGG genes, respectively, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).