Pseudohypoaldosteronism Type I Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10179 NR3C2 81479,81479 Order Options and Pricing
SCNN1A 81406,81479
SCNN1B 81406,81479
SCNN1G 81406,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10179Genes x (4)81479 81406, 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

Pseudohypoaldosteronism type I (PHAI) is a group of disorders characterized by mineralocorticoid resistance in the kidneys and/or other mineralocorticoid target tissues. Patients have high levels of plasma aldosterone and renin, but also develop excessive salt wasting (Tajima et al. 2017. PubMed ID: 28804203). PHAI is classified into three forms. The systemic form results in severe neonatal onset life-threatening salt wasting in multiple organs including sweat glands, salivary glands, the colonic epithelium, and lungs. The renal form is characterized by aldosterone resistance that is restricted to the kidneys. The third form is a type of secondary PHA1 with an unknown mechanism, which is associated with urinary tract infections (UTI) and/or urinary tract malformations.

Genetics

The systemic form of PHAI is an autosomal recessive disorder that is caused by defects in any one of three genes (SCNN1A, SCNN1B and SCNN1G) (Chang et al. 1996. PubMed ID: 8589714; Hansson et al. 1995. PubMed ID: 7550319). These three genes (each with 12 coding exons) encode the alpha, beta and gamma subunits of the epithelial sodium channel (ENaC), respectively. These amiloride-sensitive channels play a key role in electrolyte transportation across epithelia in many organs.

The renal form of PHAI is an autosomal dominant disorder that is caused by defects in the NR3C2 gene (Geller et al. 1998. PubMed ID: 9662404). The NR3C2 gene (eight coding exons) encodes the mineralocorticoid receptor, which is important in regulating the sodium level in the body.

Genetic defects spread throughout the SCNN1A, SCNN1B, SCNN1G and NR3C2 genes include missense and various truncating variants (nonsense, splicing variants and small deletions/insertions) (Human Gene Mutation Database). Gross deletions and duplications in these genes appear to be rare as only a few large deletions have been documented in SCNN1A, SCNN1B, and NR3C2 to date (Human Gene Mutation Database). Of note, de novo pathogenic variants are common in NR3C2 (Pujo et al. 2007. PubMed ID: 16972228).

Clinical Sensitivity - Sequencing with CNV PGxome

In a multi-center European cohort of Pseudohypoaldosteronism type I (PHAI) patients, pathogenic NR3C2 variants were identified in 87% of kindreds with familial autosomal dominant PHAI and in 81% of patients with a sporadic renal presentation (Pujo et al. 2007. PubMed ID: 16972228).

The diagnostic rate of the systemic form of PHAI by testing the three genes SCNN1A, SCNN1B and SCNN1G in a large cohort of patients is unavailable because studies in the literature only include a limited number of cases.

Gross deletions and duplications in these genes appear to be rare as only a few large deletions have been documented in SCNN1A, SCNN1B, and NR3C2 to date (Human Gene Mutation Database). No large deletions or deletions have yet been found involving SCNN1G.

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 pseudohypoaldosteronism type I (PHAI).

Genes

Official Gene Symbol OMIM ID
NR3C2 600983
SCNN1A 600228
SCNN1B 600760
SCNN1G 600761
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Chang et al. 1996. PubMed ID: 8589714
  • Geller et al. 1998. PubMed ID: 9662404
  • Hansson et al. 1995. PubMed ID: 7550319
  • Human Gene Mutation Database (Bio-base).
  • Pujo et al. 2007. PubMed ID: 16972228
  • Tajima et al. 2017. PubMed ID: 28804203

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

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.

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