Hereditary Coproporphyria via the CPOX 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
11211 CPOX 81405 81405,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11211CPOX81405 81405, 81479 $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 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Hereditary Coproporphyria (HCP) is a metabolic disorder due to impairment of the sixth enzyme, coproporphyrinogen oxidase, in the heme biosynthesis pathway. Neurovisceral symptoms occur in about 80% of HCP cases and include nausea, hypertension, vomiting, tachycardia, constipation, hyponatremia, seizures and neuropsychiatric attacks. In severe cases, attacks may progress to respiratory failure and death. Cutaneous symptoms are present in less than half of HCP patients, but may include photosensitivity resulting in skin blistering similar to patients with porphyria cutanea tarda and variegate porphyria (Whatley et al. 2009; Lamoril et al. 2001). Symptom onset occurs after puberty with women being more susceptible. Pre-symptomatic diagnosis is helpful in preventing acute attacks through avoidance of triggers including alcohol, certain drugs, infections, steroid hormones, and fasting (Bissell et al. 1993). Early diagnosis of HCP is also important as affected individuals are at increased risk for development of hepatocellular carcinoma. Genetic testing is helpful in the differential diagnosis of HCP from other forms of porphyria (Bissell et al. 1993; www.porphyriafoundation.com).

Harderoporphyria is a severe subtype of HCP with individuals being homozygous or compound heterozygous for pathogenic variants in the CPOX gene. Harderoporphyria is characterized by neonatal hemolytic anemia, jaundice, hepatomegaly, and splenomegaly with disease onset in infancy (Bissell et al. 1993).

Genetics

HCP and Harderoporphyria are inherited in autosomal dominant and recessive manners respectively due to pathogenic variants in the CPOX gene. Penetrance is incomplete for HCP with environmental and physiological factors increasing the risk for acute attacks. In one study, of the 32 individuals biochemically diagnoses with HCP, only 10 experienced acute attacks (Rosipal et al. 1999). Harderoporphyria is fully penetrant.

Pathogenic variants are found throughout the coding region of the CPOX gene with missense variants being present in over half of cases. Splice site, nonsense, and small insertions/deletions have also been reported in the CPOX gene. Two gross deletions involving exon 5 and exons 4-7 have been reported (Bissell et al. 1993). There is no clear genotype phenotype correlation in HCP patients (Lamoril et al. 2001).The CPOX gene encodes the coproporphyrinogen oxidase enzyme which catalyzes coproporphyrinogen III to protoporphyrinogen which is the sixth step in the heme biosynthesis pathway (Bissell et al. 1993).

Clinical Sensitivity - Sequencing with CNV PGxome

In two studies with individuals having a clinical and biochemical diagnosis of HCP, 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 have only been reported in rare cases (Whatley et al. 2009).

Testing Strategy

This test provides full coverage of all coding exons of the CPOX 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 present with blistering due to photosensitivity and neurovisceral symptoms consistent with HCP. Patients with HCP present with increased porphyrins (primarily coproporphyrin III), aminolevulinic acid (ALA), and porphobilinogen (PBG) in urine. Plasma porphyrin show fluorescent peaks at 620nm although levels may appear normal (Whatley et al. 2009; Bissell et al. 1993).

Gene

Official Gene Symbol OMIM ID
CPOX 612732
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hereditary Coproporphyria AD 121300

Citations

  • American Porphyria Foundation
  • Bissell D.M. et al. 1993. PubMed ID: 23236641
  • Lamoril J. et al. 2001. American Journal of Human Genetics. 68: 1130-8. PubMed ID: 11309681
  • Rosipal R. et al. 1999. Human Mutation. 13: 44-53. PubMed ID: 9888388
  • 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.
Total Price: $
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