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P450 Oxidoreductase Deficiency via the POR 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
8213 POR 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8213POR81479 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

  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Cytochrome P450 oxidoreductase (POR) deficiency (PORD) is a rare disorder of steroidogenesis with a wide range of clinical presentations. To date, approximate 100 diagnosed patients have been reported (Pandey and Flück 2013). Patients with PORD can be apparently healthy, but all have some degree of steroid deficiency, mainly due to combined indirect impairment of 21-hydroxylase, 17α-hydroxlyase, and aromatase in adrenal gland and gonads. Disordered sex development can occur in both males and females. Ambiguous genitalia is a common finding in affected neonates. Severely affected patients may also have congenital multiple malformations, including craniosynostosis, brachycephaly, severe midface hypoplasia, radiohumeral synostosis, and multiple joint contractures, which has been considered a recessive form of Antley-Bixler syndrome (ABS). Dominantly inherited ABS usually manifests with skeletal malformations with normal steroid metabolism, and is caused by gain-of-function mutations in FGFR2 (Huang et al. 2005; Cragun et al. 2009; Pandey and Flück 2013).

Genetics

The POR gene encodes P450 oxidoreductase (POR), which is a ubiquitously expressed enzyme. POR acts as an obligatory electron donor to all cytochrome P450 enzymes, including CYP17A1, CYP21A2, CYP19A1, and CYP51A1. Therefore, clinical symptoms of PORD result from combined indirect impairment of cytochrome P450 enzymes secondary to mutations in the POR gene (Pandey and Flück 2013).

PORD is an autosomal recessive disorder. Over 40 disease-causing variants have been identified and are scattered throughout the gene, including missense, nonsense, splicing site mutations, small deletions/insertions, and large deletions/duplications (Krone et al. 2012; Huang et al. 2005). Nearly all severally affected patients carried a loss-of-function variant, whereas patients having two missense mutations usually present with milder skeletal malformations (Krone et al. 2012). The p.Ala287Pro variant (in exon 8) is the most common mutation found in patients with European ancestry, and the p.Arg457His variant (in exon 11) is most frequently reported in the Japanese population (Krone et al. 2012; Huang et al. 2005).

Reduced P450 oxidoreductase enzyme activity associated with non-disease causing polymorphisms has been reported and may contribute to some variation in drug metabolism. However, it is not well established (Pandey and Flück 2013) and is not the purpose of this test.

Clinical Sensitivity - Sequencing with CNV PGxome

In a cohort of 30 patients with PORD, 28 patients (~93%) were identified to carry at least one causative POR variant (Krone et al. 2012).

To date, four gross deletions and one duplication have been reported to be causative for PORD (Krone et al. 2012; Soneda et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the POR 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

Individuals with clinical symptoms and biochemical findings consistent with PORD. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in POR.

Gene

Official Gene Symbol OMIM ID
POR 124015
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Cragun D, Hopkin RJ. 2009. Cytochrome P450 Oxidoreductase Deficiency. 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: 20301592
  • Huang N, Pandey AV, Agrawal V, Reardon W, Lapunzina PD, Mowat D, Jabs EW, Vliet G Van, Sack J, Flück CE, Miller WL. 2005. Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. Am. J. Hum. Genet. 76: 729–749. PubMed ID: 15793702
  • Krone N, Reisch N, Idkowiak J, Dhir V, Ivison HE, Hughes BA, Rose IT, O’Neil DM, Vijzelaar R, Smith MJ, MacDonald F, Cole TR, et al. 2012. Genotype-phenotype analysis in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. J. Clin. Endocrinol. Metab. 97: E257–267. PubMed ID: 22162478
  • Pandey AV, Flück CE. 2013. NADPH P450 oxidoreductase: structure, function, and pathology of diseases. Pharmacol. Ther. 138: 229–254. PubMed ID: 23353702
  • Soneda S, Yazawa T, Fukami M, Adachi M, Mizota M, Fujieda K, Miyamoto K, Ogata T. 2011. Proximal promoter of the cytochrome P450 oxidoreductase gene: identification of microdeletions involving the untranslated exon 1 and critical function of the SP1 binding sites. J. Clin. Endocrinol. Metab. 96: E1881–1887. PubMed ID: 21900384

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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