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Chronic Granulomatous Disease via the NCF2 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
8167 NCF2 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8167NCF281479 81479,81479 $990 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 platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Megan Piazza, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Chronic granulomatous disease (CGD) is an inherited immunodeficiency characterized by repeated infections with bacterial and fungal pathogens and formation of granulomas. CGD immunodeficiency is due to an impairment of the NADPH oxidase complex resulting in an inability to generate superoxide in phagocytic cells to lyse pathogens (Song et al. 2011). Common pathogens include Staphylococcus aureus, Pseudomonas species, Candida albicans, Aspergillus species, and Nocardia species. Pneumonia, granuloma formation within gastrointestinal and genitourinary tracts, and failure to thrive are hallmark symptoms of the disorder. In severe cases, granulomas can lead to abscess formation and organ failure. Treatments include long courses of antimicrobials to ward off infections (Leiding and Holland 2012). Simultaneous administration of antimicrobials and corticosteroids may be used to resolve colitis associated with heightened inflammatory responses to infection (Leiding and Holland 2012; Song et al. 2011). Patients with CGD should avoid areas where fungal spores are common such as mulch, gardens, and yard waste. Approximately one in 200,000 newborns in the US is affected with CGD (Winkelstein et al 2000). Genetic testing can aid in differential diagnosis of CGD from other disorders associated with granuloma formation and hyperinflammation such as cystic fibrosis, hyper IgE syndrome, Crohn’s disease, allergic bronchopulmonary aspergillosis, and glucose 6-phosphate dehydrogenase deficiency (Song et al. 2011).

Genetics

CGD is primarily inherited in an X-linked manner through mutations in the CYBB gene. Autosomal recessive forms of CGD also occur through mutations in the CYBA, NCF1, NCF2, and NCF4 genes (Roos and de Boer 2014). Pathogenic variants in the NCF2 gene account for about 17% of autosomal recessive cases and 6% of all CGDs. The majority of causative variants to date are truncating with deletion, nonsense, splice site, and insertion variants accounting for 18%, 21%, 22%, and 5% of cases. Gross deletions and missense variants account for 10% and 24% of cases (Roos et al. 2010; Gentsch et al. 2009; Köker et al. 2009). Pathogenic variants occur throughout the coding region with the majority being present within the TRP1-4 domain at the N-terminus (Roos et al. 2010). The NCF2 gene encodes the p67phox protein which is a subunit of the NADPH oxidase enzyme. This complex is essential for the production of superoxide which is central for intracellular killing of pathogens in phagocytes (Song et al. 2011).

Clinical Sensitivity - Sequencing with CNV PGxome

In a series of 40 autosomal recessive CGD families with known reductions in dihydrorhodamine oxidation in neutrophils, mutations in the NCF2 gene were found in 15% of cases (Köker et al. 2009). Analytical sensitivity is ~90% for detection of causative mutation in the NCF2 gene with gross deletions being found in about 10% of cases (Roos et al. 2010).

Testing Strategy

This test provides full coverage of all coding exons of the NCF2 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

Oxidative burst test (Nitroblue tetrazolium or dihydrorhodamine) indicating impaired superoxide production, and recurrent fungal and bacterial infections are characteristic of CGD. Patients may also present with elevated acute phase reactants such as erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) (Song et al. 2011). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in NCF2.

Gene

Official Gene Symbol OMIM ID
NCF2 608515
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Gentsch M, Kaczmarczyk A, Leeuwen K van, Boer M de, Kaus-Drobek M, Dagher M-C, Kaiser P, Arkwright PD, Gahr M, Rösen-Wolff A, Bochtler M, Secord E, et al. 2010. Alu-repeat-induced deletions within the NCF2 gene causing p67- phox -deficient chronic granulomatous disease (CGD). Human Mutation 31: 151–158. PubMed ID: 19953534
  • Köker MY, Leeuwen K van, Boer M de, Çelmeli F, Metin A, Özgür TT, Tezcan I, Sanal  Ö., Roos D. 2009. Six different CYBA mutations including three novel mutations in ten families from Turkey, resulting in autosomal recessive chronic granulomatous disease. European Journal of Clinical Investigation 39: 311-319. PubMed ID: 19292887
  • Köker MY, Sanal  Ö., Leeuwen K van, Boer M de, Metin A, Patiroglu T, Özgür TT, Tezcan I, Roos D. 2009. Four different NCF2 mutations in six families from Turkey and an overview of NCF2 gene mutations. European Journal of Clinical Investigation 39: 942–951. PubMed ID: 19624736
  • Leiding JW, Holland SM. 2012. Chronic Granulomatous Disease. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 22876374
  • Roos D, Kuhns DB, Maddalena A, Bustamante J, Kannengiesser C, Boer M de, Leeuwen K van, Köker MY, Wolach B, Roesler J, Malech HL, Holland SM, Gallin JI, Stasia MJ. 2010. Hematologically important mutations: The autosomal recessive forms of chronic granulomatous disease (second update). Blood Cells, Molecules, and Diseases 44: 291–299. PubMed ID: 20167518
  • Roos D., de Boer M. 2014. Clinical and experimental immunology. 175: 139-49. PubMed ID: 24016250
  • Song E. et al. 2011. Clinical and molecular allergy : CMA. 9: 10. PubMed ID: 21624140
  • Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, Malech HL, Holland SM, Ochs H, Quie P, Buckley RH, Foster CB, Chanock SJ, Dickler H. 2000. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 79: 155–169. PubMed ID: 10844935

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

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


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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