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Congenital Fibrinogen Deficiency Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10119 FGA 81479,81479 Order Options and Pricing
FGB 81479,81479
FGG 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10119Genes x (3)81479 81479(x6) $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder, affecting about 1 in a million people, with wide variability in clinical presentation from asymptomatic to life-threatening bleeds. CFDs can be subdivided into type I (afibrinogenemia and hypofibrinogenemia) and type II deficiencies (dysfibrinogenemia and hypo-dysfibrinogenemia). Type I deficiencies are defined by individuals having reduced activity and levels of fibrinogen whereas type II individuals have normal fibrinogen levels but impaired function (Acharya and Dimichele 2008). Afibrinogenemia, the most severe form of CFD, typically presents in the neonatal period with umbilical cord bleeding being the most characteristic of disease. Bleeding tendencies are variable, but include life-threatening spontaneous and trauma related bleeds. Patients with hypofibrinogenemia have a milder disease course, as loss of fibrinogen protein is less severe than individuals with afibrinogenemia. Bleeding episodes in these individuals occur later in life often occur after trauma or surgery. Patients with dysfibrinogenemia are primarily asymptomatic, but may experience bleeding after trauma or child birth (de Moerloose et al. 2013). Unlike type I deficiencies, individuals with type II deficiencies have been reported to be at increased risk of thrombosis (Morris et al. 2009). Acquired fibrinogen deficiencies have been found in individuals with liver disease and autoantibodies (Kujovich 2005 ; Dear et al. 2007). Genetic testing is helpful in differential diagnosis of other rare bleeding disorders, distinguishing inherited and acquired forms, and for diagnosis of asymptomatic hypofibrinogenemia and dysfibrinogenemia patients prior to surgery. Treatment options include fibrinogen concentrates, cryoprecipitate, and fresh frozen plasma (Acharya and Dimichele 2008).

Genetics

CFD is caused through mutations in the FGA, FGB, or FGG genes. Together these genes encode the hexameric glycoprotein fibrinogen. Onset of afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia can occur through pathogenic variants in any of the three fibrinogen genes. Afibrinogenemia is inherited in an autosomal recessive manner with null variants accounting for the majority of causative variants. Hypofibrinogenemia and dysfibrinogenemia are both inherited in an autosomal dominant manner with reduced disease penetrance predominantly due to missense variants (de Moerloose et al. 2013; Hanss and Biot 2001). Severity is directly correlated to the degree of impaired fibrinogen level and function. Pathogenic variants for afibrinogenemia and hypofibrinogenemia can overlap with patients homozygous for the variant presenting with afibrinogenemia. Thus, asymptomatic individuals with hypofibrinogenemia often are carriers for afibrinogenemia (Acharya and Dimichele 2008). See individual test descriptions for additional information on the molecular biology of each gene. Fibrinogen is synthesized in the liver as a disulphide linked hexamer comprised of two heterotrimers consisting of one alpha, beta, and gamma chain. Fibrinogen is converted into fibrin by thrombin to promote blood clot formation through platelet bridging (Acharya and Dimichele 2008).

Clinical Sensitivity - Sequencing with CNV PGxome

In a database of 617 CFD patients, pathogenic variants in the FGA, FGB, and FGG genes account for 58%, 13%, and 29% of cases, respectively (Hanss and Biot 2001). Analytical sensitivity is >95% for detection of causative variants in the FGB and FGG. Deletions have not been reported in the FGG gene and only once in the FGB gene (Liu et al. 1985). Analytical sensitivity for the FGA gene is >80% as the majority of causative variants are detectable by this method. Large deletions in the FGA gene have been reported for afibrinogenemia (Neerman-Arbez et al. 1999; Vu et al. 2007).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates have decreased levels of fibrinogen antigen and activity (less than 0.5 g L-1) for type I CFD. Type II individuals present with discrepancies between antigen and activity measurements. All coagulation tests that depend on fibrin as an end point, PT, PPT, TT, and reptilase time are typically prolonged. Patients with a family history of hypofibrinogenemia and dysfibrinogenemia are ideal candidates for testing (Acharya and Dimichele 2008).

Genes

Official Gene Symbol OMIM ID
FGA 134820
FGB 134830
FGG 134850
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Afibrinogenemia, congenital AR 202400

Related Test

Name
PGxome®

Citations

  • Acharya SS, Dimichele DM. 2008. Rare inherited disorders of fibrinogen. Haemophilia 14: 1151–1158. PubMed ID: 19141154
  • de Moerloose P, Casini A, Neerman-Arbez M. 2013. Congenital fibrinogen disorders: an update. Semin. Thromb. Hemost. 39: 585–595. PubMed ID: 23852822
  • Dear A, Brennan SO, Sheat MJ, Faed JM, George PM. 2007. Acquired dysfibrinogenemia caused by monoclonal production of immunoglobulin lambda light chain. Haematologica 92: e111–117. PubMed ID: 18024387
  • Hanss M, Biot F. 2001. A database for human fibrinogen variants. Ann. N. Y. Acad. Sci. 936: 89–90. PubMed ID: 11460527
  • Kujovich JL. 2005. Hemostatic defects in end stage liver disease. Crit Care Clin 21: 563–587. PubMed ID: 15992673
  • Liu CY, Koehn JA, Morgan FJ. 1985. Characterization of fibrinogen New York 1. A dysfunctional fibrinogen with a deletion of B beta(9-72) corresponding exactly to exon 2 of the gene. J. Biol. Chem. 260: 4390–4396. PubMed ID: 3156856
  • Morris TA, Marsh JJ, Chiles PG, Magaña MM, Liang N-C, Soler X, Desantis DJ, Ngo D, Woods VL Jr. 2009. High prevalence of dysfibrinogenemia among patients with chronic thromboembolic pulmonary hypertension. Blood 114: 1929–1936. PubMed ID: 19420351
  • Neerman-Arbez M, Honsberger A, Antonarakis SE, Morris MA. 1999. Deletion of the fibrinogen [correction of fibrogen] alpha-chain gene (FGA) causes congenital afibrogenemia. J. Clin. Invest. 103: 215–218. PubMed ID: 9916133
  • Vu D, Neerman-Arbez M. 2007. Molecular mechanisms accounting for fibrinogen deficiency: from large deletions to intracellular retention of misfolded proteins. J. Thromb. Haemost. 5 Suppl 1: 125–131. PubMed ID: 17635718

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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