2.1 Congenital Afibrinogenemia

Mutations in the FGB gene can lead to congenital afibrinogenemia, a condition that causes excessive bleeding due to the absence of fibrinogen protein in the blood. Most FGB gene mutations that cause this condition lead to an abnormally short blueprint for protein formation (mRNA). If any fibrinogen Bβ chain is produced, it is nonfunctional. Some mutations in the FGB gene result in the formation of a protein that cannot be released from the cell, making the protein effectively nonfunctional. Because this condition occurs when both copies of the FGB gene are altered, there is a complete absence of functional fibrinogen Bβ chain. Without the Bβ subunit, the fibrinogen protein is not assembled, which results in the absence of fibrin. As a result, blood clots do not form in response to injury, leading to excessive bleeding.

2.2 Other Disorders

Mutations in one or both copies of the FGB gene can cause other bleeding disorders known as hypofibrinogenemia, dysfibrinogenemia, or hypodysfibrinogenemia.

Hypofibrinogenemia is a condition characterized by decreased levels of fibrinogen in the blood. This condition is caused by mutations that reduce but do not eliminate the production of the fibrinogen Bβ chain. People with hypofibrinogenemia can have bleeding problems that vary from mild to severe. Generally, the less fibrinogen in the blood, the more severe the bleeding problems are.

Dysfibrinogenemia is a condition characterized by abnormally functioning fibrinogen, although the protein is present at normal levels. This condition is usually caused by mutations that change a single protein building block (amino acid) in the fibrinogen Bβ chain. These mutations alter the function of the fibrinogen protein and, depending on the functional change, can lead to excessive bleeding or abnormal blood clotting (thrombosis).

Hypodysfibrinogenemia is a condition characterized by low levels of abnormally functioning fibrinogen protein in the blood. As in dysfibrinogenemia, this condition can result in excessive bleeding or thrombosis.