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Steroid-Resistant Nephrotic Syndrome and Coenzyme Q10 Deficiency via the COQ8B/ADCK4 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
8185 COQ8B 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8185COQ8B81479 81479,81479 $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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Nephrotic syndrome is a genetically heterogeneous disease defined by proteinuria, hypoalbuminemia, hyperlipidemia, and edema (Benoit et al. 2010; Santín et al. 2011; Saleem 2012). 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. Diffuse mesangial sclerosis (DMS) is the other important histological feature associated with SRNS. The clinical courses of SRNS vary greatly with a wide range of age at onset from birth to adulthood.

COQ8B/ADCK4-associated SRNS develops through Coenzyme Q10 deficiency (Ashraf et al. 2013). Recessive mutations in COQ8B resulted in reduced CoQ10 levels and reduced mitochondrial respiratory enzyme activity in cells isolated from individuals with SRNS and transformed lymphoblasts. Early diagnosis is important because it may represent a form of SRNS that can potentially be treated by CoQ10 supplementation.

Genetics

COQ8B-associated SRNS is an autosomal recessive disorder (Ashraf et al. 2013). The COQ8B gene encodes the aarF domain containing kinase 4, which interacts with members of the CoQ10 biosynthesis pathway in podocytes. So far, genetic defects of COQ8B found in SRNS include missense, nonsense mutations and small deletion/insertions (Human Gene Mutation Database). Exon-level large deletions involving COQ8B have not been reported.

All of proteins encoded by SRNS-associated genes are localized to the podocytes, which are essential in maintaining the glomerular filtration barrier. Regarding protein function and location in podocytes, COQ8B belongs to both slit diaphragm-associated proteins and mitochondrial proteins (Malaga-Dieguez et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

Detection rate of pathogenic variants in the COQ8B gene in a large cohort of patients with SRNS is unknown in the literature because documented COQ8B pathogenic variants have only been reported in limited cases. Analytical sensitivity should be high as all reported mutations are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the COQ8B 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 SRNS, especially when CoQ10 biosynthesis disruption is indicated. Testing is also indicated for family members of patients who have known mutations in the COQ8B gene. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in COQ8B.

Gene

Official Gene Symbol OMIM ID
COQ8B 615567
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Nephrotic syndrome, type 9 AR 615573

Citations

  • Ashraf S, Gee HY, Woerner S, Xie LX, Vega-Warner V, Lovric S, Fang H, Song X, Cattran DC, Avila-Casado C, Paterson AD, Nitschké P, Bole-Feysot C, Cochat P, Esteve-Rudd J, Haberberger B, Allen SJ, Zhou W, Airik R, Otto EA, Barua M, Al-Hamed MH, Kari JA, Evans J, Bierzynska A, Saleem MA, Böckenhauer D, Kleta R, El Desoky S, Hacihamdioglu DO, Gok F, Washburn J, Wiggins RC, Choi M, Lifton RP, Levy S, Han Z, Salviati L, Prokisch H, Williams DS, Pollak M, Clarke CF, Pei Y, Antignac C, Hildebrandt F. 2013. ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption. J. Clin. Invest. 123: 5179–5189.  PubMed ID: 24270420
  • Benoit G. et al. 2010. Pediatric Nephrology (berlin, Germany). 25: 1621-32. PubMed ID: 20333530
  • Human Gene Mutation Database (Bio-base).
  • Malaga-Dieguez L, Susztak K. 2013. ADCK4 “reenergizes” nephrotic syndrome. J. Clin. Invest. 123: 4996–4999. PubMed ID: 24270414
  • Saleem M.A. 2013. Pediatric Nephrology (berlin, Germany). 28: 699-709. PubMed ID: 22782578
  • Santín S. et al. 2011. Clinical Journal of the American Society of Nephrology : Cjasn. 6: 1139-48. 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


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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