Congenital Erythropoietic Porphyria via the UROS 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
11789 UROS 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11789UROS81479 81479(x2) $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

  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

Congenital Erythropoietic Porphyria (CEP), also known as Günther’s disease, is a metabolic disorder due to impairment of the fourth enzyme, uroporphyrinogen III synthase (UROS), in the heme biosynthetic pathway. Symptom onset is variable and corollary to the degree of UROS activity and amount of sun exposure. In severe cases, infants present at birth with skin blistering, hydrops fetalis, and are prone to secondary dermal infections which can lead to scarring. Other symptoms include corneal ulcers, reddish-brown coloring of teeth, mild bone loss, hemolytic anemia and bone marrow expansion. Milder cases of CEP present in adulthood with cutaneous photosensitivity (Katugampola et al. 2012). Vitamin D deficiency can be a secondary effect of CEP due to avoidance of sun exposure. Treatments for CEP include avoidance of sun exposure, vitamin D supplementation, and transfusions if hemolytic anemia is severe. Bone marrow transplantation is currently the only curative therapy. Genetic testing is helpful in the differential diagnosis of CEP from other types of porphyria, epidermolysis bullosa, and myelodysplastic syndrome (Erwin et al. 2013; Karim et al. 2015).

Genetics

CEP is inherited in an autosomal recessive manner through pathogenic variants in the UROS gene. Clinical phenotype is related to the degree of UROS activity with severe individuals having undetectable enzymatic levels. Biallelic pathogenic variants in the UROS gene are fully penetrant with the majority of cases presenting during infancy. Missense pathogenic variants occur in the majority of cases and have been reported throughout the coding region. The c.217T>C (p.Cys73Arg) variant is present in about a third of cases and is the most commonly found pathogenic variant in the UROS gene (Fortian et al. 2009; Erwin et al. 2013; Warner et al. 2002). Splice site alterations, small insertions/deletions, and promoter variants have also been reported in a minority of cases of CEP (Solis et al. 2001; Xu et al. 1995). Gross deletions encompassing one or more exons have only been reported in one case (Katugampola et al. 2012). The UROS gene encodes the uroporphyrinogen III synthase with catalyzes hydroxymethylbilane to uroporphyrinogen III in the heme biosynthetic pathway. Deposition of porphyrin isomers in tissues become photo-activated leading to oxygen radical formation and damage (Karim et al. 2015).

Clinical Sensitivity - Sequencing with CNV PGxome

In a series of unrelated patients with CEP, pathogenic variants in the UROS gene were identified in 24 of 27 cases (Katugampola et al. 2012). Analytical sensitivity should be high as nearly all reported variants are detectable by sequencing. Only one case of a gross deletion encompassing exons 2-3 has been reported and is not detectable by sequencing (Katugampola et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the UROS 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 for testing include individuals with non-immune hydrops fetalis and cutaneous photosensitivity. Biochemical findings indicative of CEP include decreased uroporphyrinogen III synthase activity in erythrocytes (typically less than 10% of normal), and increased urinary uroporphyrin I and coproporphyrin I isomers (Erwin et al. 1993; Katugampola et al. 2012). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in UROS.

Gene

Official Gene Symbol OMIM ID
UROS 606938
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Porphyria, Congenital Erythropoietic AR 263700

Citations

  • Erwin A. et al. 2013. Congenital Erythropoietic Porphyria. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 24027798
  • Fortian A. et al. 2009. Biochemistry. 48: 454-61. PubMed ID: 19099412
  • Karim Z. et al. 2015. Clinics and Research in Hepatology and Gastroenterology. 39: 412-25. PubMed ID: 26142871
  • Katugampola R.P. et al. 2012. The British Journal of Dermatology. 167: 901-13. PubMed ID: 22816431
  • Solis C. et al. 2001. The Journal of Clinical Investigation. 107: 753-62. PubMed ID: 11254675
  • Warner C.A. et al. 1992. The Journal of Clinical Investigation. 89: 693-700. PubMed ID: 1737856
  • Xu W. et al. 1995. The Journal of Clinical Investigation. 95: 905-12. PubMed ID: 7860775

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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