Congenital Erythropoietic Porphyria via the UROS Gene

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  • Clinical Features and Genetics
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
2037 UROS$750.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

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).

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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).


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).

Testing Strategy

This test involves bidirectional sequencing using genomic DNA of all coding exons of the UROS gene plus ~20 bp of flanking non-coding DNA on each side and coverage of promoter mutations present at ~200bp upstream of the transcription initiation site. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.

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).


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


Name Inheritance OMIM ID
Porphyria, Congenital Erythropoietic 263700

Related Tests

Acute Intermittent Porphyria via the HMBS Gene
Erythropoietic Protoporphyria via the FECH Gene
Hereditary Coproporphyria via the CPOX Gene
Porphyria Cutanea Tarda Type II/Hepatoerythropoietic Porphyria via the UROD Gene
X-linked Sideroblastic Anemia via the ALAS2 Gene


Genetic Counselors
  • 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
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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