Pseudohypoaldosteronism Type II via the CUL3 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
11219 CUL3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11219CUL381479 81479(x2) $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.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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 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

Clinical Features and Genetics

Clinical Features

Pseudohypoaldosteronism type II (PHAII) is a rare monogenic disorder of renal electrolyte handling featured by hypertension (due to increased renal salt reabsorption), hyperkalaemia (due to reduced renal K+ excretion, despite normal glomerular filtration and aldosterone secretion) and metabolic acidosis (due to reduced renal H+ secretion) (Wilson et al. 2001; Boyden et al. 2012). PHAII has a range of disease severity and age of onset. Pseudohypoaldosteronism type IIE (OMIM# 614496) is caused by defects in CUL3. CUL3-related PHAII develops at an average age at nine and represents the most severe end of disease compared with that caused by mutations in WNK1, WNK4 and KLHL3.

Genetics

Pseudohypoaldosteronism type II (PHAII) can be inherited in an autosomal dominant or recessive manner and has been associated with defects in four genes (WNK1, WNK4, KLHL3 and CUL3) (Wilson et al. 2001; Boyden et al. 2012). In particular, pseudohypoaldosteronism type IIE (PHA2E) is an autosomal dominant disorder caused by mutations (predominantly de novo) in the CUL3 gene. CUL3 has 16 coding exons that encode a member of the cullin protein family. Notably, to date, all documented PHAII-causing CUL3 mutations result in an aberrant splicing of exon 9 regardless of mutation location within the vicinity of this region (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

In a cohort of 52 pseudohypoaldosteronism type II (PHAII) families including 126 affected subjects, 17 families (about 33%) were found to have CUL3 mutations (Boyden et al. 2012).

No large deletions or duplications have been found in CUL3 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the CUL3 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 are patients with pseudohypoaldosteronism type II. Testing is also indicated for family members of patients who have known CUL3 mutations.

Gene

Official Gene Symbol OMIM ID
CUL3 603136
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Pseudohypoaldosteronism, type IIE AD 614496

Citations

  • Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR, Tikhonova IR, Bjornson R, Mane SM, Colussi G, Lebel M, Gordon RD, et al. 2012. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature 482: 98-102. PubMed ID: 22266938
  • Human Gene Mutation Database (Bio-base).
  • Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, et al. 2001. Human hypertension caused by mutations in WNK kinases. Science 293: 1107-1112. PubMed ID: 11498583

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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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