Steroid-Resistant Nephrotic syndrome via the WT1 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 10677 | WT1 | 81405 | 81405,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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
Nephrotic syndrome is a renal disease with clinical features that include proteinuria, hypoalbuminemia, hyperlipidemia, and edema (Benoit et al. Pediatr Nephrol 25(9):1621–1632, 2010). Approximately 20% of cases of this disease 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 of onset from birth to adulthood. WT1 defects can cause both syndromic (such as Wilms’ tumor and Frasier syndrome) and isolated SRNS. WT1-caused isolated SRNS (OMIM# 256370) can be congenital, infantile, or childhood-onset (Santín et al. Clin J Am Soc Nephrol 6(5):1139-1148, 2011). In addition, WT1 defects commonly cause diffuse mesangial sclerosis (DMS).
Genetics
Dominant de novo WT1 variants represent a minor cause of sporadic (nonfamilial) SRNS with an age of onset from birth through childhood (Santín et al., 2011; Ruf et al. Kidney Int 66(2):564-570, 2004; Mucha et al. Pediatr Res 59(2):325-331, 2006). The WT1 gene has 10 exons and encodes the Wilms’ tumor 1 protein, one of the major regulators of early gonadal and kidney development. WT1 variants associated with nephrotic syndrome include missense, splicing site variants, and small deletions, accounting for approximately 9-13% of sporadic (nonfamilial) SRNS patients with an age of onset of 18 years or younger (Mucha et al., 2006; Santín et al., 2011). Notably, these variants have been found almost exclusively in exons 8 and 9, which code for zinc finger domains 2 and 3, respectively (Mucha et al., 2006; Benoit et al., 2010).
Clinical Sensitivity - Sequencing with CNV PG-Select
WT1 variants have been found in 9-13% of sporadic (nonfamilial) SRNS patients with an age of onset of 18 years or younger (Mucha et al. Pediatr Res 59(2):325-331, 2006; Santín et al. Clin J Am Soc Nephrol 6(5):1139-1148, 2011).
Thus far, no gross deletions or duplications involving WT1 have been shown to cause steroid-resistant nephrotic syndrome. Gross deletions have been shown to cause Wilms tumor (Human Gene Mutation Database).
Testing Strategy
This test provides full coverage of all coding exons of the WT1 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 sporadic SRNS patients with age of onset from birth through childhood, especially when the NPHS1 and NPHS2 genes are normal (Santín et al., 2011). In particular, in cases for which diffuse mesangial sclerosis (DMS) can be determined by renal histology, WT1 should be one of the candidate genes to be tested (Benoit et al., 2010). Testing is also indicated for family members of patients who have known WT1 variants.
Candidates for this test are sporadic SRNS patients with age of onset from birth through childhood, especially when the NPHS1 and NPHS2 genes are normal (Santín et al., 2011). In particular, in cases for which diffuse mesangial sclerosis (DMS) can be determined by renal histology, WT1 should be one of the candidate genes to be tested (Benoit et al., 2010). Testing is also indicated for family members of patients who have known WT1 variants.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| WT1 | 607102 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Nephrotic syndrome, type 4 | AD | 256370 |
Related Test
| Name |
|---|
| Wilms Tumor via the WT1 Gene |
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
- 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
- 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
- Human Gene Mutation Database (Bio-base).
- Mucha, B. et al. (2006). "Mutations in the Wilms' tumor 1 gene cause isolated steroid resistant nephrotic syndrome and occur in exons 8 and 9." Pediatr Res 59(2):325-331. PubMed ID: 16439601
- Mucha, B. et al. (2006). "Mutations in the Wilms' tumor 1 gene cause isolated steroid resistant nephrotic syndrome and occur in exons 8 and 9." Pediatr Res 59(2):325-331. PubMed ID: 16439601
- Ruf, R. et al. (2004). "Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome." Kidney Int 66(2):564-570. PubMed ID: 15253707
- 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
- 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
- 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
- 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
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
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