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Complement Component 3 Glomerulopathy (C3G) Sequencing Panel

The eleven genes evaluated in this panel include: C3, C8A, CD46 (MCP), CFB, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, and CFI.

Background:

Complement component 3 glomerulopathy (C3G) is caused by uncontrolled activation of the alternative complement pathway (AP) resulting in abnormal deposits of C3 within the glomerular basement membrane (GBM) with little to no immunoglobulin.  Depending on the character and distribution of the GBM deposits C3G is further subdivided into C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). C3G typically shows an MPGN pattern of injury, but other injury patterns are also possible.  Autoantibodies or mutations that affect activators or regulators of the AP are detected in up to 80% of patients. Decay of C3 convertase (C3 nephritic factor) is particularly common. C3G is commonly preceded by an infection, which appears to act as an exogenous trigger. Approximately 50% of patients slowly progress to end-stage renal disease (ESRD) within 10 to 15 years.  Defective regulation of AP is thought in large part to be due to decreased activity of complement factor H (CFH), a key inhibitory regulator of the AP.  Mutations in the C-terminal region of the CFH gene are associated with aHUS, while mutations in the N-terminal region CFH are associated with C3G.1,2 Mutations in patient with C3GN/DDD have been reported in following genes encoding complement and complement-regulatory proteins:  C3, CFB, CFH, CFHR5, CFI, and MCP (CD46), and chromosomal rearrangements of CHFR1-5.3

Indications for testing:

Renal biopsy with morphologic features of C3G

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Test Details:

Genes in this panel: C3, C8A, CD46 (MCP), CFB, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, and CFI

Methods:

Next Generation Sequencing (NGS)

Direct/Sanger Sequencing (Big Dye Terminator)

Performance:

Coverage: >99.8% of targeted areas (exons +/- 10bp to include splice junctions)

Depth: 98.7% at >20x (average 210)

Frequency:  Can be performed bi-weekly (depending on receipt of samples to be tested)

Turn around time: 3 months

Cost of test:  $2500.00

Specimen Requirements:

Peripheral blood:  At least 2ml in lavender top (EDTA) or DNA PaxGene tube

Extracted DNA (quantity): 100ng total extracted

Shipping Instructions:

Peripheral blood: Ship in a protective container at room temperature.

DNA: Ship in a protective container at room temperature.

Use Arkana Laboratories FedEx number to pay for the shipping charges (FedEx #229571460).

Attention: Arkana Laboratories Molecular Division

10810 Executive Center Drive, Suite 100

Little Rock, AR 72211

Phone: (501) 604-2695

References:

  1. Riedl M, et al. C3 Glomerulopathy. Pediatr Nephrol 2016 Apr. [Epub ahead of print];
  2. Barbour TD, et al. Update on C3 glomerulopathy. Nephrol Dial Transplant 2014;0:1-9
  3. Bu F, et al. High-Throughput Genetic Testing for Thrombotic Microangiopathies and C3

Glomerulopathies.  J Am Soc Nephrol 2015;27:1245-1253)

Contact information:

Arkana Laboratories Molecular Division

10810 Executive Center Drive, Suite 100

Little Rock, AR 72211

Email: support@arkanalabs.com

Phone: (501) 604-2695

Fax: (501) 604-2699

 

Co-Director: Chris Larsen, MD

Co-Director: Jon D. Wilson, MD

Lab Manager: Marjorie Beggs, PhD