Test ID: FIBNG    
Congenital Fibrinogen Disorders, FGA, FGB, and FGG Genes, Next-Generation Sequencing, Varies

Genetic confirmation of congenital disorders of fibrinogen with the identification of an alteration in FGA, FGB, or FGG that is known or suspected to cause disease

Testing for close family members of an individual with a diagnosis of afibrinogenemia/hypofibrinogenemia or dysfibrinogenemia/hypodysfibrinogenemia

This test is not intended for prenatal diagnosis

This test detects pathogenic alterations within the FGA, FGB, and FGG genes to delineate the underlying molecular defect in a patient with a laboratory diagnosis of congenital afibrinogenemia/hypofibrinogenemia or dysfibrinogenemia/hypodysfibrinogenemia.

The gene targets for this test are:

Gene name (transcript): FGA (GRCh37 [hg19] NM_021871)

Chromosomal location: 4q31.3

Gene name (transcript): FGB (GRCh37 [hg19] NM_005141)

Chromosomal location: 4q31.3

Gene name (transcript): FGG (GRCh37 [hg19] NM_000509)

Chromosomal location: 4q32.1

The laboratory workup for a congenital fibrinogen disorder begins with global coagulation screening assays.

In afibrinogenemia, prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin clotting time (TT) may be infinitely prolonged in afibrinogenemia.

In hypofibrinogenemia, TT is more sensitive than PT or aPTT for both quantitative and qualitative defects in fibrinogen.(1) Reptilase time (RT) maybe performed in addition to or instead of TT in samples known or suspected to contain heparin, which artificially prolongs TT.

PT, aPTT, and TT have poor sensitivity for mild fibrinogen deficiency or dysfunction. Further screening and identification of a mild fibrinogen deficiency or dysfibrinogenemia requires a clottable fibrinogen assay (typically Clauss-method based, eg, FIBTP / Fibrinogen, Plasma) to further test fibrinogen function as well as an immunologic (antigentic) assay (FIBAG / Fibrinogen Antigen, Plasma) to detect the quantity of fibrinogen present. Hypofibrinogenemia is indicated by a proportional decrease of functional and immunoreactive fibrinogen. Dysfibrinogenemia is indicated by a discrepancy between functional and immunoreactive fibrinogen.

Genetic testing for a congenital disorder of fibrinogen is indicated if:

-Coagulation tests indicate a quantitative or functional defect in fibrinogen

-Acquired causes of fibrinogen deficiency or dysfunction have been excluded (eg, thrombin clotting time [TT] may be prolonged by the presence of heparin, prior exposure to bovine thrombin, and high concentrations of serum proteins, as in multiple myeloma)

• Informed Consent for Genetic Testing
• Informed Consent for Genetic Testing (Spanish)
• Rare Coagulation Disorder Patient Information

Custom Sequence Capture and Targeted Next-Generation Sequencing (NGS) Followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing When Appropriate