DNA icon

Erythropoietic Protoporphyria via the FECH 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
8289 FECH 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8289FECH81479 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

Erythropoietic protoprophyria (EPP) is an inborn error of heme biosynthesis resulting in cutaneous photosensitivity. Symptoms include acute painful photosensitivity with stinging and burning sensations upon sunlight exposure but without blistering. Chronic permanent skin lesions, anemia, iron deficiency, cholelithiasis, chronic liver disease are potentially life threatening secondary symptoms of EPP (Lecha et al. 2009). EPP onset is during the first year of life, but mean diagnosis age is 22 underlying the difficulties in accurately diagnosing EPP (Wahlin et al. 2010). Genetic testing can be helpful in the differential diagnosis of EPP from phototoxic drug reactions, hydroa vacciniforme, solar urticarial, contact dermatitis, angioedema and other forms of porphyria. Standard treatments include avoidance of sun exposure and beta carotene therapy.

Genetics

EPP is inherited in an autosomal recessive manner through mutations in the FECH gene. In greater than 90% of cases, a pathogenic variant is co-inherited in trans with the hypomorphic variant c.315-48T>C (IVS3-48C) (Balwani et al. 2012). Patients homozygous for the c.315-48C>T variant have been reported to have EPP in rare cases (Whatley et al. 2004), but the penetrance is low. The c.315-48C>T variant, which reduces FECH transcript levels through generation of a cryptic acceptor splice site, leads to nonsense mediated decay and lower FECH protein levels (Gouya et al. 2006; Gouya et al. 2002). Pathogenic variants reported in trans to the c.315-48C>T variant are missense, splice site alterations, small insertion/deletions, and nonsense mutations making up 32%, 22%, 19%, and 14% of EPP mutations (Gouya et al. 2006). The minor allele frequency for the c.315-48C>T variant is 43%, 31%, 11%, 2.7%, and <1% in Japanese, southeast Asian, Caucasian French, North African, and African American populations with EPP being nearly absent in the later ethic cohorts. Gross deletions in the FECH gene have been identified in ~10% of cases of EPP (Whatley et al. 2007). An X-linked form of protoporphyria representing ~2% of cases has been reported to occur through gain of function mutations in the ALAS2 gene (Balwani et al. 2013). Somatic mutations have been reported in the FECH gene in patients with myelodysplasia (Aplin et al. 2001). The FECH protein catalyzes the insertion of ferrous iron into protoporphyrin IX to form heme. When protoporphyrin accumulates in tissues it becomes photo-activated resulting in excess energy to be transferred to oxygen. This leads to heightened reactive oxygen species causing cellular damage and disease (Lecha et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

Causative mutations in the FECH gene were found in 140 of 151 patients with protoporphyia with the remaining 11 demonstrating X-linked forms through mutation in the ALAS2 gene (Balwani et al. 2013). Analytical sensitivity for detection of FECH mutations is ~90% as gross deletions cannot be detected by this method and are responsible for ~10% of EPP cases (Whatley et al. 2007; Gouya et al. 2006).

Testing Strategy

This test provides full coverage of all coding exons of the FECH 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).

This test also includes coverage of the following pathogenic variants: c.-252_-251delAG, c.-252A>G, c.-251G>C, c.315-67G>A and c.315-48T>C.

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 displaying painful photosensitivity with erythema and burning without blisters are hallmark characteristics of EPP. Plasma fluorescence peaks at 634nm confirms presence of high free protoporphrin levels. Ideal candidates have biochemical evidence demonstrating impaired FECH activity (Lecha et al. 2009). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in FECH.

Gene

Official Gene Symbol OMIM ID
FECH 612386
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Erythropoietic Protoporphyria AR 177000

Citations

  • Aplin C, Whatley SD, Thompson P, Hoy T, Fisher P, Singer C, Lovell CR, Elder GH. 2001. Late-onset erythropoietic porphyria caused by a chromosome 18q deletion in erythroid cells. Journal of investigative dermatology 117: 1647–1649. PubMed ID: 11886534
  • Balwani M, Bloomer J, Desnick R. 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
  • Balwani M, Bloomer J, Desnick R. 2013. X-Linked Protoporphyria. 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: 23409301
  • Gouya L, Martin-Schmitt C, Robreau A-M, Austerlitz F, Silva V Da, Brun P, Simonin S, Lyoumi S, Grandchamp B, Beaumont C, others. 2006. Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria. The American Journal of Human Genetics 78: 2–14. PubMed ID: 16385445
  • Gouya L, Puy H, Robreau A-M, Bourgeois M, Lamoril J, Silva VD, Grandchamp B, Deybach J-C. 2002. The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. Nature Genetics 30: 27–28. PubMed ID: 11753383
  • Lecha M, Puy H, Deybach J-C. 2009. Erythropoietic protoporphyria. Orphanet Journal of Rare Diseases 4: 19. PubMed ID: 19744342
  • Wahlin S, Floderus Y, Stål P, Harper P. 2011. Erythropoietic protoporphyria in Sweden: demographic, clinical, biochemical and genetic characteristics: EPP in Sweden. Journal of Internal Medicine 269: 278–288. PubMed ID: 20412370
  • Whatley SD, Mason NG, Holme SA, Anstey AV, Elder GH, Badminton MN. 2007. Gene Dosage Analysis Identifies Large Deletions of the FECH Gene in 10% of Families with Erythropoietic Protoporphyria. Journal of Investigative Dermatology 127: 2790–2794. PubMed ID: 17597821
  • Whatley SD, Mason NG, Khan M, Zamiri M, Badminton MN, Missaoui WN, Dailey TA, Dailey HA, Douglas WS, Wainwright NJ, Elder GH. 2004. Autosomal recessive erythropoietic protoporphyria in the United Kingdom: prevalence and relationship to liver disease. J. Med. Genet. 41: e105. PubMed ID: 15286165

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

loading Loading... ×

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: $
×
Copy Text to Clipboard
×