DNA icon

Primary Familial and Congenital Polycythemia (PFCP) via the EPOR 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
EPOR 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8441EPOR81479 81479,81479 $990 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 platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

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

For Sanger Sequencing click here.

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.


Genetic Counselors


  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

Primary familial and congenital polycythemia (PFCP), also known as familial erythrocytosis, is a disorder characterized by heightened red blood cell levels. Clinical symptoms range and may include headaches, dizziness, nosebleeds, and shortness of breath. PFCP may be asymptomatic, but it has been associated with predisposition to cardiovascular problems and abnormal clotting (Gordeuk et al. 2005; Huang et al. 2010). There are four forms of familial polycythemia defined by which gene is mutated: type 1-EPOR, type-2 VHL, type 3-EGLN1, and type 4-EPAS1 (Hussein et al. 2012). Erythrocytosis may also be acquired due to long term high altitude exposure, cardiac disorders characterized by hypoxia, chronic lung disease, and sleep apnea. PFCP symptoms mirror a second disorder, Polycythemia Vera, which is due to mutations in the JAK2 gene. Unlike PFCP, patients with Polycythemia Vera are at heightened risk for developing myeloid proliferative cancers (Etheridge et al. 2014). Phlebotomy has been shown to relieve clinical symptoms. Genetic testing is helpful in differential diagnosis of acquired and inherited forms as well as distinct inherited subtypes of erythrocytosis (Gordeuk et al. 2005).


PFCP is inherited in an autosomal dominant manner through mutations in the EPOR gene. Three other forms of familial polycythemia are inherited in an autosomal recessive manner through mutations in the VHL, EGLN1, and EPAS1 genes. Approximately twenty-five mutations have been identified in the EPOR gene to date with the majority being truncating or frameshift mutations within the c-terminus of the protein (Huang et al. 2010; Kralovics et al. 1997; Forget et al. 2000; Al-Sheikh et al. 2008). Two reports have identified missense mutations in the EPOR gene in individuals diagnosed with PFCP, but the functional significance of these mutations is still unclear (Le Couedic et al. 1996; Huang et. al. 2010). No gross deletions or duplications have been reported. The EPOR gene encodes the erythropoietin receptor and binds erythropoietin, an essential cytokine to promote terminal differentiation of erythrocytes. Truncating mutations in the c-terminus of the EPOR gene lead to loss of the intracellular cytoplasmic tail of the receptor. Upon ligand binding, truncated receptors have prolonged signaling due to loss of the negative regulatory domain resulting in hypersensitivity to erythropoietin (Huang et al. 2010; Gordeuk et al. 2005).

Clinical Sensitivity - Sequencing with CNV PGxome

Analytical sensitivity should be high because all mutations reported are detectable by this method. Clinical sensitivity is estimated to be <50% with one report indicating only 12% (5 of 43) patients having a mutation within the EPOR gene in patients diagnosed with PFCP (Kralovics and Prchal 2001).

No gross deletions or duplications have been reported in EPOR (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the EPOR 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

Patients with PFCP present with erythrocytosis without splenomegaly, low serum Epo levels, normal hemoglobin oxygen affinities, elevate hemoglobin levels, normal vitamin B12 levels and Epo hypersensitivity (Gordeuk et al. 2005). Ideal candidates have a family history for PFCP.


Official Gene Symbol OMIM ID
EPOR 133171
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Familial Erythrocytosis, 1 AD 133100


  • Al-Sheikh M, Mazurier E, Gardie B, Casadevall N, Galacteros F, Goossens M, Wajcman H, Prehu C, Ugo V. 2008. A study of 36 unrelated cases with pure erythrocytosis revealed three new mutations in the erythropoietin receptor gene. Haematologica 93: 1072–1075. PubMed ID: 18492694
  • Etheridge SL, Cosgrove ME, Sangkhae V, Corbo LM, Roh ME, Seeliger MA, Chan EL, Hitchcock IS. 2014. A novel activating, germline JAK2 mutation, JAK2R564Q, causes familial essential thrombocytosis. Blood 123: 1059–1068. PubMed ID: 24381227
  • Forget BG, Degan BA, Arcasoy MO. 2000. Familial polycythemia due to truncations of the erythropoietin receptor. Transactions of the American Clinical and Climatological Association 111: 38. PubMed ID: 10881330
  • Gordeuk VR, Stockton DW, Prchal JT. 2005. Congenital polycythemias/erythrocytoses. Haematologica 90: 109–116. PubMed ID: 15642677
  • Huang LJ, Shen Y-M, Bulut GB. 2010. Advances in understanding the pathogenesis of primary familial and congenital polycythaemia. British Journal of Haematology 148: 844–852. PubMed ID: 20096014
  • Hussein K, Granot G, Shpilberg O, Kreipe H. 2013. Clinical utility gene card for: familial polycythaemia vera. European Journal of Human Genetics 21: PubMed ID: 23032109
  • Kralovics R, Indrak K, Stopka T, Berman BW, Prchal JF, Prchal JT. 1997. Two new EPO receptor mutations: truncated EPO receptors are most frequently associated with primary familial and congenital polycythemias. Blood 90: 2057–2061. PubMed ID: 9292543
  • Kralovics R, Prchal JT. 2001. Genetic heterogeneity of primary familial and congenital polycythemia. American journal of hematology 68: 115–121. PubMed ID: 11559951
  • Le Couedic J-P, Mitjavila M-T, Villeval J-L, Feger F, Gobert S, Mayeux P, Casadevall N, Vainchenker W. 1996. Missense mutation of the erythropoietin receptor is a rare event in human erythroid malignancies. Blood 87: 1502–1511. PubMed ID: 8608241


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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

loading Loading... ×


An error has occurred while calculating the price. Please try again or contact us for assistance.

View Ordering Instructions

1) Select Test Method (Platform)

1) Select Test Type

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.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
Copy Text to Clipboard