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Hemophilia C via the F11 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
F11 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7079F1181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

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

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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

Hemophilia C, also known as Factor XI deficiency, is a bleeding disorder affecting an estimated one in 1,000,000 individuals. It most frequently found in Ashkenazi Jews with one in 450 individuals being affected. Unlike hemophilia A and B, both genders are equally affected. Hemophilia C patients are typically asymptomatic with the first bleeding episodes being present following trauma or surgical procedures (Seligsohn et al. 2009). Joint bleeds are uncommon but patients are more prone to bruising, nosebleeds, and blood in the urine. Women may experience menorrhagia and prolonged bleeding following childbirth. Preventive measures such as plasma and recombinant FVIIa infusions may be used prior to surgery to limit bleeding (Salomon 2006). Antifibrinolytic agents may be used for milder procedures including tooth extractions and colonoscopies (Duga and Salomon 2013).

Genetics

Hemophilia C is primarily an autosomal recessive disorder with autosomal dominant cases being reported in individuals with mild bleeding with incomplete penetrance (Mtchell et al. 2006). Disease is caused by mutations within the F11 gene (Seligsohn 2009; Duga and Salomon 2013). Within Ashkenazi Jews, two founder mutations account for >90% of cases: c.403G>T resulting in p.Glu135* and c.901T>C resulting in p.Phe301Leu and affecting the catalytic domain of the FXI protein (Asakai et al.1989). Other missense mutations throughout the F11 gene are causative in >90% of cases in other ethnic backgrounds (Mitchell et al. 2006; Zucker et al. 2007). Factor XI is a zymogen which becomes activated by thrombin to promote coagulation at sites of injury. Because FXI functions as a homodimeric protein complex, dominant negative mutations have been described leading to the disease and inherited in an autosomal dominant manner (Dai et al. 2011).

Clinical Sensitivity - Sequencing with CNV PG-Select

Based on the literature, we estimate that sequencing will detect at least one likely causative mutation in >90% of hemophilia C cases. Larger deletions, not detectable by sequencing, have been reported in <5% cases. Mutations in the F11 gene are the only documented causes of hemophilia C (Mitchell et al. 2006).

Testing Strategy

This test provides full coverage of all coding exons of the F11 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for testing typically present with bleeding episodes that may occur following trauma or surgery, especially in tissues with high local fibrinolytic activity. Prolonged aPPT and FXI activity in plasma less than 20 IU/dL are common symptoms. Family members of patients known to have F11 mutations are also candidates (Duga and Salomon 2013). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in F11.

Gene

Official Gene Symbol OMIM ID
F11 264900
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hereditary Factor XI Deficiency Disease 612416

Related Tests

Name
Bleeding Disorders Panel
Coagulation Factor Deficiency Panel

Citations

  • Asakai R, Chung DW, Ratnoff OD, Davie EW. 1989. Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations. Proc Natl Acad Sci U S A 86: 76677671. PubMed ID: 2813350
  • Dai L, Rangarajan S, Mitchell M. 2011. Three dominant-negative mutations in factor XI-deficient patients. Haemophilia 17: e919922. PubMed ID: 21457405
  • Duga S, Salomon O. 2013. Congenital factor XI deficiency: an update. Semin. Thromb. Hemost. 39: 621631. PubMed ID: 23929304
  • Mitchell M, Mountford R, Butler R, Alhaq A, Dai L, Savidge G, Bolton-Maggs PHB. 2006. Spectrum of factor XI (F11) mutations in the UK population 116 index cases and 140 mutations. Human Mutation 27: 829829. PubMed ID: 16835901
  • Salomon O, Steinberg DM, Seligshon U. 2006. Variable bleeding manifestations characterize different types of surgery in patients with severe factor XI deficiency enabling parsimonious use of replacement therapy. Haemophilia 12: 490493. PubMed ID: 16919078
  • Seligsohn U. 2009. Factor XI deficiency in humans. J. Thromb. Haemost. 7 Suppl 1: 8487. PubMed ID: 19630775
  • Zucker M, Zivelin A, Landau M, Salomon O, Kenet G, Bauduer F, Samama M, Conard J, Denninger M-H, Hani A-S, Berruyer M, Feinstein D, et al. 2007. Characterization of seven novel mutations causing factor XI deficiency. Haematologica 92: 13751380. PubMed ID: 18024374

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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View Ordering Instructions

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2) Select Additional Test Options

No Additional Test Options are available for this test.

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