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Hemophilia A via the F8 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
3077 F8 81407 81407,81406 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3077F881407 81406(x1), 81407(x1) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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

Hemophilia A is the most common inherited bleeding disorder worldwide with 1 in 5,000 males being affected. Symptoms include bleeding into joints, blood into the urine, bruising, nosebleeds, prolonged bleeding from cuts, and gastrointestinal tract or urinary tract hemorrhaging. In affected individuals, impaired F8 protein function leads to a diminished clotting potential. Severity ranges from mild to moderate to severe and is directly correlated to the degree of impaired F8 function. The frequency of mild, moderate, and severe forms are 50%, 10%, and 40% respectively (Graw et al. 2005). Many mild cases go unnoticed until later in life when an individual incurs surgery or trauma. Recurrent bleeding in joints becomes painful and is indicative of chronic synovitis (Konkle et al. 2011). F8 is produced by liver sinusoidal cells and endothelial cells outside the liver. This protein circulates bound to von Willebrand Factor (VWF) in an inactive state. In response to injury, F8 is released from VWF and interacts other coagulation factors to form clots. Hemophilia A and von Willebrand Disease (Test #449) are phenotypically similar due to the cooperation between F8 and von Willebrand Factor to promote clotting. Hemophilia A may be treated with desmopressin or recombinant F8 to help with clotting. These treatments are particularly important for individuals with Hemophilia A undergoing dental or medical surgeries to prevent excessive bleeding (Konkle et al. 2013). Hemophilia A is clinically similar to Hemophilia B, but treatment for each condition requires transfusion of different proteins to restore clotting functions. Genetic testing can further be used to distinguish between acquired and inherited forms of Hemophilia A (Keeney et al. 2011).

Genetics

Hemophilia A is an X-linked recessive disorder characterized by many different mutations in the F8 gene. Males are primarily affected, but homozygous females for F8 mutations have also been shown to exhibit clinical features. To date, over two thousand mutations in the F8 gene have been described in patients with Hemophilia A (Kemball-Cook et al. 1998) suggesting each family bears its own mutation (Lakich et al. 1993). Point and small deletions or insertions account for about 60% of all cases, while inversions at intron 1 or 22 lead to 2-3% and 45% of cases respectively. A third of patients have no family history of Hemophilia with onset due to de novo mutations (Konkle et al. 2011). F8 protein circulates bound to von Willebrand Factor (VWF) in an inactive state. In response to injury F8 is released from VWF and interacts with other coagulation factors to form clots. Causative mutations in the F8 gene lead to a loss of protein clotting function (Graw et al. 2005).

Clinical Sensitivity - Sequencing with CNV PG-Select

Mutations in the F8 gene are the only known cause of Hemophilia A. Analytical sensitivity is ~60% as inversions are not detected by this sequencing method and are the causative mutations for Hemophilia A in ~40% of cases.

Testing Strategy

This test provides full coverage of all coding exons of the F8 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

This testing will NOT detect commonly found inversions in intron 1 and 22.

Indications for Test

This test is for individuals with symptoms and assays of hemostasis (prolonged PPT, low Factor VIII levels) that suggest Hemophilia A. Female carrier status cannot be definitively diagnosed by coagulation testing. Most patients have a positive family history. Males are predominant candidates as disease is X-linked recessive (Konkle et al. 2011).

Gene

Official Gene Symbol OMIM ID
F8 300841
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hemophilia A, Congenital XL 306700

Related Tests

Name
Bleeding Disorders Panel
Coagulation Factor Deficiency Panel

Citations

  • Graw J, Brackmann H-H, Oldenburg J, Schneppenheim R, Spannagl M, Schwaab R. 2005. Haemophilia A: from mutation analysis to new therapies. Nature Reviews Genetics 6: 488–501. PubMed ID: 15931172
  • Keeney S, Cumming T, Jenkins PV, O’Donnell JS, Nash MJ. 2011. Clinical utility gene card for: Haemophilia A. European Journal of Human Genetics 19: PubMed ID: 21654722
  • Kemball-Cook G, Tuddenham EG, Wacey AI. 1998. The factor VIII structure and mutation resource site: HAMSTeRS version 4. Nucleic acids research 26: 216–219. PubMed ID: 9399839
  • Konkle BA, Josephson NC, Nakaya Fletcher SM, Thompson AR. 1993. Hemophilia A. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle,. PubMed ID: 20301578
  • Lakich D, Kazazian HH, Antonarakis SE, Gitschier J. 1993. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nat. Genet. 5: 236–241. PubMed ID: 8275087

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

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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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