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Congenital Factor XIII deficiency via the F13A1 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
11315 F13A1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11315F13A181479 81479,81479 $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

Factor XIII deficiency is a rare bleeding disorder that is typically severe. The first and most characteristic symptom seen in about 80% of patients is umbilical cord bleeding following birth. Other frequent symptoms include superficial bruising, subcutaneous hematomas, spontaneous abortions in early pregnancy and joint bleeds leading to hemarthrosis (Schroeder and Kohler 2013). Intracranial hemorrhage appears in one in four patients and is a leading cause of death. Unlike other rare bleeding disorders, mucosal tract bleeding is a common symptom and seen in over a third of affected individuals. This is due to the dual role of Factor XIII in crosslinking fibrin chains to promote clotting and crosslinking fibronectin and collagen to enhance gut wound healing. Factor XIII deficiency is also acquired through development of autoantibodies against FXIII protein (Hayashi et al. 2012; Sugiyama et al. 2013). Genetic testing may aid in differential diagnosis of acquired and congenital forms of the deficiency. Affected patients with congenital factor XIII deficiency may be treated with fresh frozen plasma, recombinant FXIII or plasma derived FXIII concentrates to mitigate symptoms (Nugent 2006; Inbal et al. 2012). These therapies fail to alleviate disease in acquired Factor XIII deficiency and require immunosuppressive drugs for treatment. Diagnosis of Factor XIII deficiency is often difficult because deficiency cannot be detected by routine global coagulation assays (Bolton-Maggs et al. 2012) and because FXIII laboratory assays must be carefully timed with blood sampling (Perez et al. 2011; Karimi et al. 2009).

Genetics

Factor XIII deficiency is inherited in an autosomal recessive manner through mutations in the F13A1 and F13B genes. Heterozygous individuals with mutations in the F13A1 gene have been reported to have milder forms of the disease with symptoms becoming apparent after trauma or surgery. The majority of Factor XIII deficiencies have causative mutations in the F13A1 gene with missense, small insertions/deletions, and splice site alterations being found in >80% of cases (Schroeder and Kohler 2013; www.f13-database.de). Mutations are found throughout the F13A1 gene and presumably alter protein folding and stability (Biswas et al. 2011). The FXIII protein is a heterotetramer consisting of two A and two B subunits (FXIII A2B2). This tetramer functions as a transglutaminase with the A subunit containing the catalytic domain and the B subunit being the carrier protein. In plasma, FXIII activation is essential for fibrin polymerization and stabilizing clots during the hemostatic process (Muszbek et al. 2011).

Clinical Sensitivity - Sequencing with CNV PGxome

Rare bleeding disorders (RBD) comprise of inherited deficiencies of coagulation factors fibrinogen, FII, FV, FV + FVIII, FVII, FX, FXI, and FXIII. Factor XIII deficiencies are found ~5% of all RBD cases. In patients with Factor XIII deficiency, F13A1 mutations are found in >80% of cases (Peyvandi et al. 2013). Analytical sensitivity should be high because nearly all mutations reported are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the F13A1 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 typically have moderate to severe bleeding episodes with umbilical cord bleeding often being the first symptom of disease. Ideal candidates have decreased FXIII functional activity assay. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in F13A1.

Gene

Official Gene Symbol OMIM ID
F13A1 134570
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Factor XIII, A Subunit, Deficiency Of AR 613225

Citations

  • Biswas A, Ivaskevicius V, Seitz R, Thomas A, Oldenburg J. 2011. An update of the mutation profile of Factor 13 A and B genes. Blood Rev. 25: 193–204. PubMed ID: 21640452
  • Bolton-Maggs PHB, Favaloro EJ, Hillarp A, Jennings I, Kohler HP. 2012. Difficulties and pitfalls in the laboratory diagnosis of bleeding disorders. Haemophilia 18 Suppl 4: 66–72. PubMed ID: 22726086
  • Factor XIII Registry Database
  • Hayashi T, Kadohira Y, Morishita E, Asakura H, Souri M, Ichinose A. 2012. A case of acquired FXIII deficiency with severe bleeding symptoms. Haemophilia 18: 618–620. PubMed ID: 22356719
  • Inbal A, Oldenburg J, Carcao M, Rosholm A, Tehranchi R, Nugent D. 2012. Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency. Blood 119: 5111–5117. PubMed ID: 22451421
  • Karimi M, Bereczky Z, Cohan N, Muszbek L. 2009. Factor XIII Deficiency. Semin. Thromb. Hemost. 35: 426–438. PubMed ID: 19598071
  • Muszbek L, Bereczky Z, Bagoly Z, Komáromi I, Katona É. 2011. Factor XIII: a coagulation factor with multiple plasmatic and cellular functions. Physiol. Rev. 91: 931–972. PubMed ID: 21742792
  • Nugent DJ. 2006. Prophylaxis in rare coagulation disorders -- factor XIII deficiency. Thromb. Res. 118 Suppl 1: S23–28. PubMed ID: 16616323
  • Perez DL, Diamond EL, Castro CM, Diaz A, Buonanno F, Nogueira RG, Sheth K. 2011. Factor XIII deficiency related recurrent spontaneous intracerebral hemorrhage: a case and literature review. Clin Neurol Neurosurg 113: 142–145. PubMed ID: 20950938
  • Peyvandi F. et al. 2013. Blood. 122: 3423-31. PubMed ID: 24124085
  • Schroeder V, Kohler HP. 2013. Factor XIII deficiency: an update. Semin. Thromb. Hemost. 39: 632–641. PubMed ID: 23929307
  • Sugiyama H, Uesugi H, Suzuki S, Tanaka K, Souri M, Ichinose A. 2013. Aggressive fatal case of autoimmune hemorrhaphilia resulting from anti-Factor XIII antibodies. Blood Coagul. Fibrinolysis 24: 85–89. PubMed ID: 23183237

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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