Liddle Syndrome and Autosomal Recessive Pseudohypoaldosteronism Type 1 via the SCNN1B 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
11649 SCNN1B 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11649SCNN1B81406 81406, 81479 $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.

For Reflex to PGxome pricing click here.

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 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

Liddle syndrome (OMIM #177200) is an inherited disorder of sodium reabsorption in the renal distal tubules characterized by severe early onset of hypertension with hypokalemia, metabolic alkalosis, low plasma renin activity, and suppressed aldosterone secretion (Botero-Velez et al. N Engl J Med 330(3):178-181, 1994; Shimkets et al. Cell 79(3):407-414, 1994). Untreated hypertension in these patients can progress with age to renal failure, heart disease or stroke.

Autosomal recessive pseudohypoaldosteronism type 1 (PHA1; OMIM #264350) is a multi-organ life-threatening disorder characterized by severe neonatal onset salt wasting and high concentrations of sodium in sweat, stool, and saliva (Chang et al. Nat Genet 12(3):248-253, 1996; Scheinman et al. N Engl J Med 340(15):1177-1187, 1999). Clinical features include hyponatremia, hyperkalaemia, metabolic acidosis, unresponsiveness to mineralocorticoid hormones, and increased plasma renin activity with high serum aldosterone concentrations. Compared with autosomal dominant PHA1, the recessive form of the disease is a more severe systemic condition with persistence into adulthood. Some patients had recurrent respiratory problems (Chang et al., 1996; Schaedel et al. J Pediatr 135(6):739-745, 1999). Genetic confirmation is essential for distinguishing autosomal recessive PHA1 from cystic fibrosis-like disease (Sheridan et al. Hum Mol Genet 14(22):3493-3498, 2005; Azad et al. Hum Mutat 30(7):1093-1103, 2009; Mora-Lopez et al. Eur J Pediatr 171(6):997-1000, 2012).

Genetics

Autosomal recessive PHA1 can be caused by mutations in any one of the three genes (SCNN1A, SCNN1B and SCNN1G) encoding the epithelial sodium channel (ENaC) while Liddle syndrome is an autosomal dominant disorder caused by mutations in SCNN1B or SCNN1G (Shimkets et al., 1994; Hansson et al. Nat Genet 11(1):76-82, 1995; Chang et al., 1996). These amiloride-sensitive channels play a key role in electrolyte transportation across epithelia in many organs. SCNN1B has 12 coding exons that encode the beta subunit of ENaC. Genetic defects located throughout the SCNN1B gene include missense, nonsense, splicing mutations and small deletion/insertions. Gross deletions within the SCNN1B gene have also been reported (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

SCNN1B mutation detection rate in a larger cohort of patients with Liddle syndrome is unavailable because these Liddle syndrome-associated SCNN1B mutations have been only reported in individual cases.

SCNN1B mutation detection rates in autosomal recessive PHA1 patients via Sanger sequencing of coding exons varied from 0% to 25% in different studies, each of which had a limited number of patients (Chang et al. Nat Genet 12(3):248-253, 1996; Kerem et al. N Engl J Med 341(3):156-162, 1999; Saxena et al. J Clin Endocrinol Metab 87(7):3344-3350, 2002; Welzel et al. Eur J Endocrinol 168(5):707-715, 2013).

Testing Strategy

This test provides full coverage of all coding exons of the SCNN1B 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.

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 Liddle syndrome or autosomal recessive PHA1. Testing is also indicated for family members of patients who have known SCNN1B mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SCNN1B.

Gene

Official Gene Symbol OMIM ID
SCNN1B 600760
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Azad, A. et al. (2009). "Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease." Hum Mutat 30(7):1093-1103. PubMed ID: 19462466
  • Botero-Velez, M. et al. (1994). “Liddle's syndrome revisited - a disorder of sodium reabsorption in the distal tubule.” N Engl J Med 330(3):178-181. PubMed ID: 8264740
  • Chang, S. et al. (1996). "Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1." Nat Genet 12(3):248-253.  PubMed ID: 8589714
  • Hansson, J. et al. (1995). "Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome." Nat Genet 11(1):76-82.  PubMed ID: 7550319
  • Human Gene Mutation Database (Bio-base).
  • Kerem, E. et al. (1999). "Pulmonary epithelial sodium-channel dysfunction and excess airway liquid in pseudohypoaldosteronism." N Engl J Med 341(3):156-162. PubMed ID: 10403853
  • Mora-Lopez, F. et al. (2012). “Novel mutation in the epithelial sodium channel causing type I pseudohypoaldosteronism in a patient misdiagnosed with cystic fibrosis.” Eur J Pediatr 171(6):997-1000. PubMed ID: 22371258
  • Saxena, A. et al. (2002). “Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes.” J Clin Endocrinol Metab 87(7):3344-3350. PubMed ID: 12107247
  • Schaedel, C. et al. (1999). "Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the alpha-subunit of the epithelial sodium channel." J Pediatr 135(6):739-745. PubMed ID: 10586178
  • Scheinman, S. et al. (1999). “Genetic disorders of renal electrolyte transport.” N Engl J Med 340(15):1177-1187. PubMed ID: 10202170
  • Sheridan, M. et al. (2005). “Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome.” Hum Mol Genet  14(22):3493-3498. PubMed ID: 16207733
  • Shimkets, R. et al. (1994). "Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel." Cell 79(3):407-414. PubMed ID: 7954808
  • Welzel, M. et al. (2013). "Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1." Eur J Endocrinol 168(5):707-715. PubMed ID: 23416952

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

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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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