Autosomal Dominant Pseudohypoaldosteronism Type 1 via the NR3C2 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 11527 | NR3C2 | 81479 | 81479,81479 | $990 | 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 platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
The Sanger Sequencing method for this test is NY State approved.
For Sanger Sequencing click here.Turnaround Time
3 weeks on average for standard orders or 2 weeks 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.
Clinical Features and Genetics
Clinical Features
Autosomal dominant pseudohypoaldosteronism type 1 (PHA1; OMIM #177735) is characterized by neonatal renal salt wasting with hyperkalaemic acidosis due to renal unresponsiveness to mineralocorticoids (Geller et al. Nature Genet 19(3): 279-281, 1998). Patients improve with age in early childhood and usually become asymptomatic with no need of treatment. An elevated aldosterone level is common in adult patients. Compared with the autosomal recessive form of PHA1, the dominant type form disease is relatively mild. Much less frequently reported, pathogenic NR3C2 mutations have also been associated with autosomal dominant early-onset hypertension with severe exacerbation in pregnancy (OMIM #605115) (Geller et al. Science 289(5476): 119-123, 2000).
Genetics
NR3C2-related PHA1 and hypertension are both inherited in an autosomal dominant manner (Geller et al., 1998; Geller et al., 2000). NR3C2 has 8 coding exons that encode the mineralocorticoid receptor, which is important in regulating the sodium level in the body. Genetic defects located throughout the NR3C2 gene include missense, nonsense, splicing mutations and small deletion/insertions (Sartorato et al. J Clin Endocrinol Metab 88(6):2508-2517, 2003; Riepe et al. J Clin Endocrinol Metab 91(11):4552-4561, 2006). Gross deletions and duplications have not been reported while complex rearrangements involving the NR3C2 gene appear to be rare (Human Gene Mutation Database). De novo mutations are common in the NR3C2 gene (Pujo et al. Hum Mutat 28(1):33-40, 2007).
Clinical Sensitivity - Sequencing with CNV PGxome
In a multi-center European cohort of PHA1 patients, NR3C2 mutations were identified in 87% of kindreds with familial autosomal dominant PHA1 and in 81% of patients with a sporadic renal presentation (Pujo et al. Hum Mutat 28(1): 33-40, 2007).
Testing Strategy
This test provides full coverage of all coding exons of the NR3C2 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
Candidates for this test can be patients with autosomal dominant PHA1 or autosomal dominant early-onset hypertension with severe exacerbation in pregnancy. Testing is also indicated for family members of patients who have known NR3C2 mutations.
Candidates for this test can be patients with autosomal dominant PHA1 or autosomal dominant early-onset hypertension with severe exacerbation in pregnancy. Testing is also indicated for family members of patients who have known NR3C2 mutations.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| NR3C2 | 600983 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Hypertension, Early-Onset, Autosomal Dominant, With Severe Exacerbation In Pregnancy | 605115 | |
| Pseudohypoaldosteronism Type 1 Autosomal Dominant | AD | 177735 |
Citations
- Geller, D. et al. (1998). “Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I.” Nature Genet 19(3): 279-281. PubMed ID: 9662404
- Geller, D. et al. (2000). “Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy.” Science 289(5476): 119-123. PubMed ID: 10884226
- Human Gene Mutation Database (Bio-base).
- Pujo, L. et al. (2007). “Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism.” Hum Mutat 28(1):33-40. PubMed ID: 16972228
- Riepe, F. et al. (2006). "Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1." J Clin Endocrinol Metab 91(11):4552-4561. PubMed ID: 16954160
- Sartorato, P. et al. (2003). “Different inactivating mutations of the mineralocorticoid receptor in fourteen families affected by type I pseudohypoaldosteronism.” J Clin Endocrinol Metab 88(6):2508-2517. PubMed ID: 12788847
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
Loading...
×
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.