Congenital Fibrinogen Deficiency via the FGG Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11333 FGG 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11333FGG81479 81479(x2) $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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 most characteristic. 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 in individuals with afibrinogenemia. Bleeding episodes in these individuals occur later in life often 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 mutations in any of the three fibrinogen genes. Afibrinogenemia is inherited in an autosomal recessive manner with null mutations accounting for the majority of causative variants. Hypofibrinogenemia and dysfibrinogenemia are inherited in an autosomal dominant manner with reduced disease penetrance predominantly due to missense mutations (de Moerloose et al. 2013). Severity of CFD is correlated with fibrinogen level and function. Asymptomatic individuals with hypofibrinogenemia often are carriers for afibrinogenemia (Acharya and Dimichele 2008). Mutations in the FGG gene account for ~30% of CFD cases with missense mutations being most prevalent and affecting assembly, secretion, and/or stability of the hexameric fibrinogen (Matsuda and Sugo 2002; Hanss and Biot 2001; Vu et al. 2007; Neerman-Arbez and de Moerloose 2007). About 70% of causative FGG mutations are associated with hypofibrinogenemia and dysfibrinogenemia instead of afibrinogenemia. Only one large deletion has been associated with the FGG gene (Human Gene Mutation Database). 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

Rare bleeding disorders (RBD) are comprised of inherited deficiencies of coagulation factors fibrinogen, FII, FV, FV + FVIII, FVII, FX, FXI, and FXIII. CFDs comprise ~8% of all RBD cases (Peyvandi et al. 2013). In patients with CFD, causative FGG mutations are found in ~30% of cases (Hanss and Biot 2001). Analytical sensitivity is >95% as the great majority of causative variants are detectable by sequencing. Only one large deletion has been reported (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the FGG gene 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 full 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 times are typically prolonged. Patients with a family history of hypofibrinogenemia and dysfibrinogenemia are ideal candidates for testing (Acharya and Dimichele 2008). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in FGG.

Gene

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

Disease

Name Inheritance OMIM ID
Afibrinogenemia, congenital AR 202400

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
  • Human Gene Mutation Database (Bio-base).
  • Kujovich JL. 2005. Hemostatic defects in end stage liver disease. Crit Care Clin 21: 563–587. PubMed ID: 15992673
  • Matsuda M, Sugo T. 2002. Structure and function of human fibrinogen inferred from dysfibrinogens. Int. J. Hematol. 76 Suppl 1: 352–360. PubMed ID: 12430881
  • 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, Moerloose P de. 2007. Mutations in the fibrinogen gene cluster accounting for congenital afibrinogenemia: an update and report of 10 novel mutations. Hum. Mutat. 28: 540–553. PubMed ID: 17295221
  • Peyvandi F. et al. 2013. Blood. 122: 3423-31. PubMed ID: 24124085
  • 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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