Hemophilia B via the F9 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7641 | F9 | 81238 | 81238,81479 | $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.
Clinical Features and Genetics
Clinical Features
Hemophilia B, also known as factor IX deficiency or Christmas disease, is the second most common type of hemophilia occurring in about one in 25,000 males. Symptoms range widely, but mainly include prolonged bleeding following dental or surgical procedures, excessive bruising, prolonged nose bleeding, deep muscle hematomas, hemarthrosis and GI bleeding (Konkle et al. 2011). Disease severity (mild, moderate, or severe) and age of diagnosis are related to the level of Factor IX clotting activity. Individuals with mild hemophilia B are often not diagnosed until later in life after abnormal bleeding occurs following trauma. Individuals with severe forms are typically diagnosed before age two and average several bleeding episodes per month. Treatment with recombinant factor IX or tranexamic acid may help promote clotting and are often used for patients undergoing surgery (Lambert et al. 2007).
Genetics
Hemophilia B is an X-linked recessive disorder characterized by mutations in the F9 gene. Males are primarily affected, but homozygous females with F9 mutations have also been documented. To date, over a thousand unique variants have been observed throughout the F9 gene with missense mutations being causative in about 75% of cases (Giannelli et al. 1998). In about 30% of cases, there is no family history of the disorder and the condition is a result of a de novo gene mutation. Mutations in the F9 promoter are associated with a specific subtype, known as hemophilia B Leyden. These individuals express low levels of F9 protein until puberty at which point F9 levels rise with increased androgen receptor and growth factor activity (Funnell et al. 2013). Factor IX is a zymogen present in the plasma. When cleaved and activated by factor Xla or factor VIIa it hydrolyzes factor X to drive coagulation.
Clinical Sensitivity - Sequencing with CNV PG-Select
Clinically, Hemophilia A is not distinguishable from Hemophilia B. With appropriate biochemical testing indicative of Hemophilia B (Factor IX activity <30%), detection of causative F9 mutations are found via DNA sequencing in ~95% of cases.
Testing Strategy
This test provides full coverage of all coding exons of the F9 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
This test is for individuals with symptoms and assays of hemostasis (prolonged PPT, low Factor IX levels) that suggest Hemophilia B. Female carrier status cannot be definitively diagnosed by coagulation testing. Most patients have a positive family history. Males are predominant candidates as the disease is X-linked.
This test is for individuals with symptoms and assays of hemostasis (prolonged PPT, low Factor IX levels) that suggest Hemophilia B. Female carrier status cannot be definitively diagnosed by coagulation testing. Most patients have a positive family history. Males are predominant candidates as the disease is X-linked.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| F9 | 300746 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Hereditary Factor IX Deficiency Disease | XL | 306900 |
Related Tests
| Name |
|---|
| Bleeding Disorders Panel |
| Coagulation Factor Deficiency Panel |
Citations
- Funnell APW, Wilson MD, Ballester B, Mak KS, Burdach J, Magan N, Pearson RCM, Lemaigre FP, Stowell KM, Odom DT, Flicek P, Crossley M. 2013. A CpG Mutational Hotspot in a ONECUT Binding Site Accounts for the Prevalent Variant of Hemophilia B Leyden. Am. J. Hum. Genet. 92: 460–467. PubMed ID: 23472758
- Giannelli F, Green PM, Sommer SS, Poon M, Ludwig M, Schwaab R, Reitsma PH, Goossens M, Yoshioka A, Figueiredo MS, Brownlee GG. 1998. Haemophilia B: database of point mutations and short additions and deletions--eighth edition. Nucleic Acids Res. 26: 265–268. PubMed ID: 9399849
- Konkle BA, Josephson NC, Nakaya Fletcher SM, Thompson AR. 2011. Hemophilia B. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviewsTM, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301668
- Lambert T, Recht M, Valentino LA, Powell JS, Udata C, Sullivan ST, Roth DA. 2007. Reformulated BeneFix: efficacy and safety in previously treated patients with moderately severe to severe haemophilia B. Haemoph. Off. J. World Fed. Hemoph. 13: 233–243. PubMed ID: 17498071
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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