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Chronic/Cutaneous Porphyria Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10219 ALAS2 81479,81479 Order Options and Pricing
CPOX 81405,81479
FECH 81479,81479
PPOX 81406,81479
UROD 81479,81479
UROS 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10219Genes x (6)81479 81405(x1), 81406(x1), 81479(x10) $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

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).

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

Porphyrias are a group of metabolic disorders caused by impairment of heme biosynthesis pathway. There are two different forms of porphyria: acute/neurovisceral and chronic/cutaneous. Symptom onset typically occurs in late childhood to adulthood. Chronic porphyrias include congenital erythropoietic porphyria (CEP), porphyria cutanea tarda (PCT), hepatoerythropoietic porphyria (HEP), hereditary coproporphyria (HCP) variegate porphyria (VP), erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP). In these patients, either blistering or non-blistering cutaneous lesions occur at sites 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 (Karim et al. 2015).

PCT is the most common form of porphyria with an occurrence of 1 in 10,000 in Europeans. Genetic testing is helpful in confirming diagnosis of chronic/cutaneous porphyria subtypes and from other cutaneous blistering conditions. Standard treatments typically involve monitoring of urinary porphyrin levels and phlebotomies to reduce iron stores. Avoidance of susceptibility factors and increased surveillance for hepatocellular carcinoma are also common for patients, especially with PCT (Liu et al. 1993). Vitamin D deficiency can be a secondary effect of chronic/cutaneous porphyria due to avoidance of sun exposure. Patients with VP and HEP also may present with acute/neurovisceral symptoms (Karim et al. 2015).

Genetics

There are currently six different forms of chronic/cutaneous porphyria caused by specific pathogenic variants in genes involved in heme biosynthesis: hereditary coproporphyria (CPOX), variegate porphyria (PPOX), porphyria cutanea tarda/hepatoerythropoietic porphyria (UROD), congenital erythropoietic protoporphyria (UROS), erythropoietic protoporphyria (FECH), and X-linked protoporphyria (ALAS2). PCT, VP, and HCP inherited in an autosomal dominant manner whereas HEP, EPP, CEP are inherited in an autosomal recessive manner. Pathogenic variants in the ALAS2 gene are associated with an X-linked recessive form of porphyria (Karim et al. 2015; Besur et al. 2014).

See individual gene test descriptions for information on molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

Detection of Pathogenic variants in the FECH gene was found in 140 of 151 patients with protoporphyia with the remaining 11 demonstrating X-linked forms through pathogenic variants in the ALAS2 gene (Balwani et al. 2012). Analytical sensitivity is ~90% as gross deletions cannot be detected by this method and are responsible for ~10% of cases (Whatley et al. 2007; Gouya et al. 2006).

In a series of 103 patients where variegate porphyria diagnosis was established by elevated fecal porphyrin measurement, decreased PPOX activity, and elevated plasma porphyrin fluorescence, pathogenic variants were identified in 96% of cases (Whatley et al. 1999). Analytical sensitivity is >95% for detection of pathogenic variants in the PPOX gene (Singal and Anderson 1993).

In two studies with individuals having a clinical and biochemical diagnosis of hereditary coproporphyria, pathogenic variants in the CPOX gene were identified in 29 of 31 and 32 of 32 patients respectively (Whatley et al. 2009; Rosipal et al. 1999). Analytical sensitivity is >95% as gross deletions in the CPOX gene have only been reported in rare cases (Whatley et al. 2009).

In a series of unrelated patients with congenital erythropoietic protoporphyria, pathogenic variants in the UROS gene were identified in 24 of 27 cases (Katugampola et al. 2012). Analytical sensitivity is >99% as all reported variants are detectable by this method. Only one case of a gross deletion encompassing exons 2-3 in the UROS gene has been reported (Katugampola et al. 2012).

In a patient cohort containing both sporadic and familial porphyria cutanea tarda, pathogenic variants in the UROD gene were identified in 131 of 248 patients (Aarsand et al. 2009). Analytical sensitivity is >95% as large deletions cannot be detected by this method and have been reported in a few cases (Mendez et al. 1998; Liu et al. 2013).

Gross deletions have been reported in <10% of erythropoietic protoporphyria cases (FECH gene), <5% of variegate porphyria cases (PPOX gene), <5% of hereditary coproporphyria cases (CPOX gene), <2% of congenital erythropoietic porphyria cases (UROS gene), and <5% of porphyria cutanea tarda cases (UROD gene). To date, gross deletions/duplications have not been reported in the ALAS2 gene.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 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

Blistering on sun exposed areas is a typical feature of patients with chronic/cutaneous porphyria. Plasma fluorescence peaks at 634nm confirms presence of high free protoporphrin levels and elevated uroporphyrin in urine are common biochemical findings (Karim et al. 2015).

Genes

Official Gene Symbol OMIM ID
ALAS2 301300
CPOX 612732
FECH 612386
PPOX 600923
UROD 613521
UROS 606938
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Aarsand A.K. et al. 2009. Clinical Chemistry. 55: 795-803. PubMed ID: 19233912
  • Balwani M. et al. 2012. Erythropoietic Protoporphyria, Autosomal Recessive. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 23016163
  • Besur S et al. 2014. Metabolites. 4: 977-1006. PubMed ID: 25372274
  • Gouya L. et al. 2006. American Journal of Human Genetics. 78: 2-14. PubMed ID: 16385445
  • 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
  • Liu L.U. et al. 2013. Porphyria Cutanea Tarda, Type II. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 23741761
  • Mendez M. et al. 1998. American Journal of Human Genetics. 63: 1363-75. PubMed ID: 9792863
  • Rosipal R. et al. 1999. Human Mutation. 13: 44-53. PubMed ID: 9888388
  • Singal A.K. and Anderson K.E.. 1993. Variegate 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: 23409300
  • Whatley S.D. et al. 1999. American Journal of Human Genetics. 65: 984-94. PubMed ID: 10486317
  • Whatley S.D. et al. 2007. The Journal of Investigative Dermatology. 127: 2790-4. PubMed ID: 17597821
  • Whatley S.D. et al. 2009. Clinical Chemistry. 55: 1406-14. PubMed ID: 19460837

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.
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