Nephrotic Syndrome (NS)/Focal Segmental Glomerulosclerosis (FSGS) Panel
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Panel CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
10417 | Genes x (72) | 81479 | 81405(x2), 81406(x4), 81407(x5), 81408(x2), 81479(x131) | $990 | Order Options and Pricing |
Pricing Comments
We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.
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).
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 (NS) is a genetically heterogeneous disease defined by proteinuria, hypoalbuminemia, hyperlipidemia, and edema (Benoit et al. 2010. PubMed ID: 20333530; Santín et al. 2011. PubMed ID: 21415313; Preston et al. 2019. PubMed ID: 29181713). It is the most common glomerular disease in children. Nephrotic syndrome in young adults and children is classified into steroid-sensitive NS (SSNS) versus steroid-resistant NS (SRNS) in terms of its response to a standardized steroid therapy. Approximately 20% of cases are 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. Hereditary FSGS can be either limited to the kidney or syndromic with features in other systems. Diffuse mesangial sclerosis (DMS) is the other important histological feature associated with SRNS. SRNS accounts for ~11% of early-onset chronic kidney disease (CKD) (Vivante and Hildebrandt. 2016. PubMed ID: 26750453). The clinical courses of NS vary greatly with a wide range of age at onset from birth to adulthood. A conclusive molecular diagnosis is necessary for better personalized treatment and accurate genetic counselling.
Genetics
The inheritance modes of NS/FSGS associated with the genes listed below can be autosomal dominant, autosomal recessive or X-linked (Sharif and Barua. 2018. PubMed ID: 29465426; Lovric et al. 2016. PubMed ID: 26507970; Preston et al. 2017. PubMed ID: 29181713). This panel also includes the genes for syndromic focal glomerulosclerosis, such as Galloway-Mowat syndrome (GAMOS) (see for example at Braun et al. 2017. PubMed ID: 28805828), and TRIM8-related early-onset epileptic encephalopathy (Assoum et al. 2018. PubMed ID: 30244534; Warren et al. 2020. PubMed ID: 32193649).
Defects in the COL4A3, COL4A4 and COL4A5 genes cause a wide spectrum of phenotypes from autosomal recessive or dominant Alport syndrome to autosomal dominant familial hematuria and thin basement membrane disease (TBMD) (see for example at Gast et al. 2016. PubMed ID: 26346198; Malone et al. 2014. PubMed ID: 25229338).
We also include the APOL1 gene in this panel, whose kidney risk alleles have a significant effect on disease susceptibility (Genovese et al. 2010. PubMed ID: 20647424; Friedman and Pollak. 2019. PubMed ID: 31710572).
The spectrum of pathogenic variants throughout these genes includes all types of genetic changes. Of note, large deletions are relatively commonly found in the COL4A3, COL4A4 and COL4A5 genes. De novo variants are common in the WT1 and TRIM8 genes.
Autosomal dominant: ACTN4, ANLN, ARHGAP24, COL4A3, COL4A4, INF2, LMX1B, MAFB, MYH9, NFKB2, PAX2, TRIM8, TRPC6, and WT1
Autosomal dominant or recessive: CD2AP
Autosomal recessive: ANKFY1, ARHGDIA, AVIL, CDK20, COQ2, COQ6, COQ8B/ADCK4, CRB2, CUBN, DAAM2, DGKE, DLC1, EMP2, FAT1, GAPVD1, GON7, ITGA3, ITGB4, ITSN1, ITSN2, KANK1, KANK2, KANK4, KAT2B, KIRREL1, LAMA5, LAMB2, MAGI2, MYO1E, NEU1, NPHS1, NPHS2, NUP107, NUP133, NUP160, NUP205, NUP93, OSGEP, PDSS2, PLCE1, PTPRO, SCARB2, SGPL1, SMARCAL1, TBC1D8B, TNS2, TP53RK, TPRKB, TTC21B, WDR4, WDR73, XPO5 and YRDC
X-linked dominant: COL4A5, COL4A6 and TBC1D8B
X-linked recessive: LAGE3
Risk gene: APOL1
Proteins encoded by the majority of NS-associated genes in the current panel are localized to the podocytes, which are essential in maintaining the glomerular filtration barrier. Regarding protein function and location in podocytes, the proteins encoded by associated genes can be divided into several subgroups as listed below (Preston et al. 2017. PubMed ID: 29181713).
Slit diaphragm-associated proteins: CD2AP, CRB2, FAT1, KIRREL1, NPHS1, NPHS2, PLCE1, and TRPC6
Nuclear proteins/transcription factors: LMX1B, MAFB, NFKB2, NUP107, NUP133, NUP160, NUP205, NUP93, PAX2, SMARCAL1, WDR4, WDR73, WT1, XPO5, and YRDC
Cytoskeletal, scaffold and membrane proteins: ACTN4, ANLN, ARHGAP24, ARHGDIA, AVIL, CDK20, CUBN, DAAM2, DLC1, EMP2, GON7, INF2, ITSN1, ITSN2 KANK1, KANK2, KANK4, KAT2B, LAGE3, MYO1E, MAGI2, OSGEP, PTPRO, TNS2, TP53RK, and TPRKB
Glomerular basement membrane-associated: COL4A3, COL4A4, COL4A5, COL4A6, ITGA3, ITGB4, LAMA5 and LAMB2
Mitochondrial proteins: COQ2, COQ6, COQ8B/ADCK4 and PDSS2
Lysosome-associated proteins: SCARB2
Metabolic and cytosolic proteins: DGKE, SGPL1 and TTC21B
Endosomal regulator RAB5 regulation: ANKFY1 and GAPVD1
Other: APOL1, MYH9, NEU1 and TRIM8
See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.
Clinical Sensitivity - Sequencing with CNV PGxome
In the largest international cohort study to date, sequencing for 27 genes known to cause steroid-resistant nephrotic syndrome (SRNS) detected a single-gene cause across 21 genes in 29.5% (526 of 1783) of families with SRNS that manifested before 25 years of age (Sadowski et al. 2015. PubMed ID: 25349199).
In our laboratory, the positive rate (i.e. test yield) is ~23%. The major positive genes (~55%) are NPHS1, NPHS2, and WT1. The COL4A3, COL4A4 and COL4A5 genes together account for ~20% of positive cases. Other less frequently found causative genes (~20%) are PLCE1, TRPC6, INF2, and LMX1B. The remaining genes together only account for ~5.0%.
Testing Strategy
This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.
This panel typically provides 99.8% coverage of all coding exons of the genes 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 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 nephrotic syndrome (NS) or focal segmental glomerulosclerosis (FSGS). This test especially aids in a differential diagnosis of similar phenotypes by analyzing multiple genes simultaneously.
Candidates for this test are patients with nephrotic syndrome (NS) or focal segmental glomerulosclerosis (FSGS). This test especially aids in a differential diagnosis of similar phenotypes by analyzing multiple genes simultaneously.
Genes
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Diseases
Related Test
Name |
---|
PGxome® |
Citations
- Assoum et al. 2018. PubMed ID: 30244534
- Benoit et al. 2010. PubMed ID: 20333530
- Braun et al. 2017. PubMed ID: 28805828
- Friedman and Pollak. 2019. PubMed ID: 31710572
- Gast et al. 2016. PubMed ID: 26346198
- Genovese et al. 2010. PubMed ID: 20647424
- Lovric et al. 2016. PubMed ID: 26507970
- Malone et al. 2014. PubMed ID: 25229338
- Preston et al. 2017. PubMed ID: 29181713
- Sadowski et al. 2015. PubMed ID: 25349199
- Santín et al. 2011. PubMed ID: 21415313
- Sharif and Barua. 2018. PubMed ID: 29465426
- Vivante and Hildebrandt. 2016. PubMed ID: 26750453
- Warren et al. 2020. PubMed ID: 32193649
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
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.