Primary Aldosteronism Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
3023 CACNA1D 81479,81479 Order Options and Pricing
CACNA1H 81479,81479
CLCN2 81479,81479
KCNJ5 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
3023Genes x (4)81479 81479 $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 PGxome Custom Panel tool.

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

For Reflex to PGxome pricing 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

Primary aldosteronism is characterized by a constitutive overproduction of aldosterone (Tevosian et al. 2019. PubMed ID: 31884735; Mulatero et al. 2013. PubMed ID: 23229280). It is the most common form of secondary hypertension and affects 8–13% of patients with hypertension. The two most common causes of primary aldosteronism are aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). While the majority of cases are sporadic, about 5% of cases are suspected to be familial, and incidence is unknown (Tevosian et al. 2019. PubMed ID: 31884735).

Known genetic syndromes featuring primary aldosteronism are autosomal dominant familial hyperaldosteronism types I, II, III, and IV with variable age of onset (mostly childhood and adolescence).

Familial hyperaldosteronism type I (FH-I; also known as glucocorticoid-remediable aldosteronism) presents a wide spectrum of clinical features. The majority of affected individuals develop severe hypertension early in life and high rates of cerebrovascular conditions while some display a mild phenotype. Patients with FH-I display increased levels of the secreted hybrid steroids 18-hydroxycortisol and 18-oxocortisol whereas hypokalaemia is seldom observed.

Familial hyperaldosteronism type II (FH-II) is a nonglucocorticoid-remediable form of primary aldosteronism. Patients present with hypertension due to increased aldosterone, often with hypokalemia. Most patients present before the age of 20 years old, but some may be as early as infancy. Spironolactone has been shown to be an effective treatment option (Scholl et al. 2018. PubMed ID: 29403011).

Familial hyperaldosteronism type III (FH-III) presents an early onset of primary aldosteronism with hypokalaemia and severe hypertension resistant to medical therapy (including spironolactone and amiloride). Patients with FH-III are characterized by bilateral adrenal hyperplasia and high levels of 18-hydroxycortisol and 18-oxocortisol.

Germline pathogenic variants in genes encoding voltage-gated calcium channels (CACNA1D and CACNA1H) can cause primary aldosteronism with or without neurologic abnormalities.

Without treatment, hypertension increases the risk of stroke, renal damage, and heart failure. This test is useful for differential diagnosis of similar phenotypes by analyzing multiple genes simultaneously.

Genetics

Germline pathogenic variants causing primary aldosteronism with autosomal dominant inheritance have been found in the CYP11B2, CLCN2, KCNJ5, CACNA1D and CACNA1H genes (Dutta et al. 2016. PubMed ID: 27485459; Mulatero et al. 2013. PubMed ID: 23229280; Scholl et al. 2018. PubMed ID: 29403011).

Familial hyperaldosteronism type I is caused by a chimeric gene of CYP11B1 and CYP11B2, which results from an unequal crossover event. Testing for chimeric CYP11B1/CYP11B2 is currently not available on our test menu. CYP11B1 encodes steroid 11β-hydroxylase.

Familial hyperaldosteronism type II is caused by CLCN2 pathogenic variants. CLCN2 encodes the ClC-2 chloride channel which is expressed in the adrenal zona glomerulosa which is consistent with this gene having a role in aldosterone production regulation. Reported cases include inherited and de novo variants (Scholl et al. 2018. PubMed ID: 29403011).

Familial hyperaldosteronism type III is caused by KCNJ5 pathogenic variants. KCNJ5 encodes the G-protein-activated inward rectifier K+ channel 4 (GIRK4, also known as inward rectifier K+ channel Kir3.4). To date, only missense changes and a small in-frame deletion have been reported in KCNJ5 to cause familial hyperaldosteronism type III. In most reported cases, the pathogenic variant is inherited from an affected parent (Mulatero et al. 2012. PubMed ID: 22203740; Scholl et al. 2012. PubMed ID: 22308486).

Familial hyperaldosteronism type IV is caused by CACNA1H pathogenic variants. CACNA1H encodes a voltage-gated calcium channel (Cav3.2) expressed in adrenal glomerulosa. A recurrent gain-of-function, missense variant (c.4647G>C, p.Met1549Val) was reported in five unrelated individuals with two cases being de novo events (Scholl et al. 2015. PubMed ID: 25907736). However, two carriers of the variant were normotensive as adults and did not have a history of hypertension. Therefore, incomplete penetrance is suggested for this gene.

To date, only a very limited number of germline missense changes have been found in CACNA1D in patients with primary aldosteronism (Scholl et al. 2013. PubMed ID: 23913001). CACNA1D encodes the α1 subunit of L-type voltage calcium channel. All reported cases have been de novo variants (Scholl et al. 2013. PubMed ID: 23913001; Strauss et al. 2018. PubMed ID: 28726809).

Large deletions and duplications are not commonly reported in any of the genes in this panel (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

KCNJ5 pathogenic variants were reported to account for about 7% of patients with familial hyperaldosteronism (Mulatero et al. 2013. PubMed ID: 23229280).

Scholl et al. sequenced the CACNA1D gene in 100 unrelated individuals with unexplained early-onset primary aldosteronism and identified two girls with de novo heterozygous gain-of-function missense variants (Scholl et al. 2013. PubMed ID: 23913001).

Scholl et al. performed exome sequencing in 40 unrelated individuals with hypertension due to primary aldosteronism with onset age by 10 years (Scholl et al. 2015. PubMed ID: 25907736). In these patients who were negative for pathogenic variants in the CYP11B2, KCNJ5, and CACNA1D genes, five probands were found to have a heterozygous for a missense pathogenic variant in the CACNA1H gene. In an additional study on this cohort of 35 remaining individuals, four individuals were heterozygous for variants in CLCN2 (Scholl et al. 2018. PubMed ID: 29403011). Analysis of an additional 45 unrelated subjects with primary aldosteronism before 20 years of age found two additional patients with CLCN2 variants.

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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with a suspected hereditary form of primary aldosteronism.

Genes

Official Gene Symbol OMIM ID
CACNA1D 114206
CACNA1H 607904
CLCN2 600570
KCNJ5 600734
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Dutta et al. 2016. PubMed ID: 27485459
  • Human Gene Mutation Database (Biobase).
  • Mulatero et al. 2012. PubMed ID: 22203740
  • Mulatero et al. 2013. PubMed ID: 23229280
  • Scholl et al. 2012. PubMed ID: 22308486
  • Scholl et al. 2013. PubMed ID: 23913001
  • Scholl et al. 2015. PubMed ID: 25907736
  • Scholl et al. 2018. PubMed ID: 29403011
  • Strauss et al. 2018. PubMed ID: 28726809
  • Tevosian et al. 2019. PubMed ID: 31884735

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.

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

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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.

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