Primary Pigmented Nodular Adrenocortical Disease via the PDE11A Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
15271 PDE11A 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15271PDE11A81479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

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

  • Hannah Cox, PhD

Clinical Features and Genetics

Clinical Features

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare disorder that causes adrenocorticotropic hormone (ATCH)-independent adrenal hyperplasia resulting in Cushing Syndrome (Manipadam et al. 2011). Cushing syndrome causes the body to have prolonged exposure to cortisol leading to obesity, severe fatigue, weak muscles, high blood pressure, high blood sugar, irritability, and anxiety. Cushing syndrome has a prevalence of 1/26,000, and PPNAD represents 2% of these cases (http://www.orpha.net/). PPNAD is often associated with Carney's complex, however, isolated PPNAD is also known to occur less frequently (Stratakis 2009). In PPNAD, the adrenal glands are small to normal sized and harbor multiple small cortical pigmented nodules. Most cases of PPNAD occur in the second and third decades of life, but it can also occur very early (e.g. 2-3 years of age), and it appears to be more frequent in females (Almeida and Stratakis 2010).

Genetics

Primary pigmented nodular adrenocortical disease is inherited in an autosomal dominant manner and can be caused by germline mutations in the PRKAR1A and PDE11A genes (Gaillard et al. 2010). The PRKAR1A gene encodes a tumor suppressor that acts as a cyclic-AMP-dependent signaling molecule. The signaling molecule phosphorylates many downstream targets that are involved in transcription, metabolism, cell cycle progression and apoptosis (Rothenbuhler and Stratakis 2010). PDE11A catalyzes the hydrolysis of cAMP and cGMP and is expressed in several endocrine tissues (Almeida and Stratakis 2010). Both PDE11A and PRKAR1A repress the activity of protein kinase A, which is involved in cellular proliferation, and both may act in concert, when mutated, to promote adrenal cortical cell proliferation (Bar-Lev and Annes 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

The clinical sensitivity of PDE11A germline mutations in patients with PPNAD is currently unknown as only a small number of individual cases have been reported.

Testing Strategy

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

This test provides full coverage of all coding exons of the PDE11A 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.

Indications for Test

Individuals with a clinical presentation of Primary Pigmented Nodular Adrenocortical Disease and individuals with a family history of disease.

Gene

Official Gene Symbol OMIM ID
PDE11A 604961
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Pigmented Nodular Adrenocortical Disease, Primary, 2 AD 610475

Citations

  • Almeida MQ, Stratakis CA. 2010. Carney complex and other conditions associated with micronodular adrenal hyperplasias. Best Practice & Research Clinical Endocrinology & Metabolism 24: 907–914. PubMed ID: 21115159
  • Bar-Lev A, Annes JP. 2012. Genetics of adrenocortical disease: an update. Current Opinion in Endocrinology & Diabetes and Obesity 19: 159–167. PubMed ID: 22476103
  • Gaillard RC, Bertherat J, Carney JA. 2010. Familial micronodular adrenocortical disease, Cushing syndrome, and mutations of the gene encoding phosphodiesterase 11A4 (PDE11A). PubMed ID: 20351491
  • Manipadam MT, Abraham R, Sen S, Simon A. 2011. Primary pigmented nodular adrenocortical disease. J Indian Assoc Pediatr Surg 16: 160–162. PubMed ID: 22121318
  • Orphanet
  • Rothenbuhler A, Stratakis CA. 2010. Clinical and molecular genetics of Carney complex. Best Practice & Research Clinical Endocrinology & Metabolism 24: 389–399. PubMed ID: 20833331
  • Stratakis CA. 2009. New genes and/or molecular pathways associated with adrenal hyperplasias and related adrenocortical tumors. Molecular and Cellular Endocrinology 300: 152–157. PubMed ID: 19063937

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

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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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