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Steroid-Resistant Nephrotic Syndrome via the NPHS2 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7765 NPHS2 81405 81405,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7765NPHS281405 81405,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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

  • Wuyan Chen, PhD

Clinical Features and Genetics

Clinical Features

Nephrotic syndrome is a renal disease defined by proteinuria, hypoalbuminemia, hyperlipidemia, and edema (Benoit et al. Pediatr Nephrol 25(9):1621–1632, 2010). Approximately 20% of cases are steroid-resistant nephrotic syndrome (SRNS), characterized by resistance to steroid treatment and rapid progression to end-stage renal failure. The prevalent histological feature of SRNS is focal segmental glomerulosclerosis (FSGS), which has been seen in approximately 60% of SRNS cases. SRNS presents with a wide range of age at onset from birth to adulthood. NPHS2-caused SRNS typically presents early in infancy and childhood (OMIM# 600995) but NPHS2 defects can also cause congenital, adolescent and adult-onset SRNS (Santín et al. Clin J Am Soc Nephrol 6(5):1139-1148, 2011).

Genetics

NPHS2-caused SRNS is an autosomal recessive disorder regardless of age at onset. NPHS2 defects are the primary cause of SRNS with age at onset from infancy through adult in both familial and sporadic cases (Santín et al., 2011). The NPHS2 gene with 8 exons encodes podocin that is crucial in the function of the glomerular filtration barrier in the kidneys. Missense, nonsense, splicing site mutations, small deletion/insertions have been found across the whole coding region of the NPHS2 gene. Large deletion/duplication and complex rearrangement have not been reported. The Western European founder mutation R138Q appears most often, accounting for up to 32% of all pathogenic NPHS2 mutations (Benoit et al., 2010; Hinkes et al. J Am Soc Nephrol 19(2):365-371, 2008). A clinically relevant correlation between NPHS2 genotype and the age of disease onset has been widely observed (Weber et al. Kidney Int 66(2):571-9, 2004; Hinkes et al. J Am Soc Nephrol 19(2):365-71, 2008; Machuca et al. Kidney Int 75(7):727-735, 2009; Santín et al. Clin J Am Soc Nephrol 6(5):344-54, 2011). Homozygous R138Q mutations or compound heterozygotes with one R138Q and one truncated mutation (nonsense or frameshift) is associated with earlier onset (mean onset Infantile and childhood onset SRNS can also be caused by defects in the NPHS1, WT1 and PLCE1 genes, though less frequently (Santín et al. 2011). Adult-onset SRNS can also be caused, less frequently, by defects in the TRPC6, INF2 and ACTN4 genes (Santín et al., 2011).

Clinical Sensitivity - Sequencing with CNV PG-Select

NPHS2 mutations have been found in about 40% of familial and 6-17% of sporadic SRNS cases (Karle et al. J Am Soc Nephrol 13(2):388–393, 2002; Caridi et al. J Am Soc Nephrol 14(5):1278–1286, 2003; Weber et al. Kidney Int 66(2):571-579, 2004; Ruf et al. J Am Soc Nephrol 15(3):722–732, 2004; Hinkes et al. J Am Soc Nephrol 19(2):365-371, 2008; Benoit et al. Pediatr Nephrol 25(9):1621–1632, 2010).

Testing Strategy

This test provides full coverage of all coding exons of the NPHS2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with SRNS of age at onset from infancy through adulthood (Santín et al., 2011). Candidates for this test are also patients with nephrotic syndrome in the first three months of life when NPHS1 is normal (Santín et al., 2011). Testing is also indicated for family members of patients who have known NPHS2 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in NPHS2.

Gene

Official Gene Symbol OMIM ID
NPHS2 604766
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Nephrotic Syndrome, Idiopathic, Steroid-Resistant AR 600995

Citations

  • Benoit, G. et al. (2010). “Hereditary nephrotic syndrome: a systematic approach for genetic testing and a review of associated podocyte gene mutations.” Pediatr Nephrol 25(9):1621-1632. PubMed ID: 20333530
  • Caridi, G. et al. (2003). “Broadening the spectrum of diseases related to podocin mutations.” J Am Soc Nephrol 14(5):1278–1286. PubMed ID: 12707396
  • Hinkes, B. et al (2008). “Specific podocin mutations correlate with age of onset in steroid-resistant nephrotic syndrome.” J Am Soc Nephrol 19(2):365-371.  PubMed ID: 18216321
  • Karle, S. et al. (2002). “Novel mutations in NPHS2 detected in both familial and sporadic steroid-resistant nephrotic syndrome.” J Am Soc Nephrol 13(2):388–393. PubMed ID: 11805166
  • Machuca, E et al. (2009) “Clinical and epidemiological assessment of steroid-resistant nephrotic syndrome associated with the NPHS2 R229Q variant.” Kidney Int. 75(7):727-35. PubMed ID: 19145239
  • Ruf, R. et al. (2004). “Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome.” J Am Soc Nephrol 15(3):722–732. PubMed ID: 14978175
  • Santín, S. et al. (2011). "Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome." Clin J Am Soc Nephrol 6(5):1139-1148.  PubMed ID: 21415313
  • Weber, S. et al. (2004). “NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence.” Kidney Int 66(2):571-579. PubMed ID: 15253708

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

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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.
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