Chronic Granulomatous Disease Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10153 CYBA 81479,81479 Order Options and Pricing
CYBB 81479,81479
NCF2 81479,81479
NCF4 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10153Genes x (4)81479 81479 $890 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 PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Chronic granulomatous disease (CGD) 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. Simultaneous administration of antimicrobials and corticosteroids may be used to resolve colitis associated with heightened inflammatory responses to infection (Leiding et al. 2012). Patients with CGD should avoid areas where fungal spores are common such as mulch, gardens, and yard waste. Approximately one in 200,000 births 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 (Leiding and Holland 2012).

Genetics

CGD is primarily inherited in an X-linked recessive manner through pathogenic variants 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 CYBB, CYBA, NCF1, NCF2, and NCF4 genes account for 70%, 5%, 20%, 5% and <1% of cases respectively (Leiding and Holland 2012; Roos et al. 2010; Roos et al. 2010). The NCF1 gene is currently not analyzed in this panel due to the presence of pseudogenes. Disease onset with individuals with X-linked CGD is ~3 years with mortality occurring in 20% compared to autosomal recessive forms with onset ~7 years and mortality occurring in 8% of cases. Together the CYBA, CYBB, NCF1, NCF2, and NCF4 genes encode the NADPH oxidase complex which is essential for superoxide production required for intracellular killing of pathogens in phagocytes (Song et al. 2011). See individual test descriptions for additional information on the molecular biology of each gene.

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the CYBB, CYBA, NCF1, NCF2, and NCF4 genes account for 70%, 5%, 20%, 5% and <1% of cases respectively (Leiding and Holland 2012). In autosomal recessive CGD families with known reductions in DHR oxidation in neutrophils, pathogenic variants in the NCF2 and CYBA gene were found in 15% and 25% of cases respectively (Roos et al. 2010). Without analysis for the NCF1 gene, clinical sensitivity for the panel is ~80% for detection of pathogenic variants in CGD patients. Analytical sensitivity is >90% for CYBB, CYBA, and NCF2 with gross deletions only being present in a few cases (Roos et al. 2010). Analytical sensitivity for NCF4 gene should also be high as all pathogenic variants to date are detectable by sequencing.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Oxidative burst test (Nitroblue tetrazolium or dihydrorhodamine) results indicating impaired superoxide production, and recurrent fungal and bacterial infections are characteristic of CGD. Patients may also present with elevated erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) (Song et al. 2011).

Genes

Official Gene Symbol OMIM ID
CYBA 608508
CYBB 300481
NCF2 608515
NCF4 601488
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Leiding JW, Freeman AF, Marciano BE, Anderson VL, Uzel G, Malech HL, DeRavin S, Wilks D, Venkatesan AM, Zerbe CS, Heller T, Holland SM. 2012. Corticosteroid therapy for liver abscess in chronic granulomatous disease. Clin. Infect. Dis. 54: 694–700. PubMed ID: 22157170
  • 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, Kuhns DB, Maddalena A, Roesler J, Lopez JA, Ariga T, Avcin T, Boer M de, Bustamante J, Condino-Neto A, Matteo G Di, He J, Hill HR, Holland SM, Kannengiesser C, Köker MY, Kondratenko I, van Leeuwen K, Malech HL, Marodi L, Nunoi H, Stasia MJ, Ventura AM, Witwer CT, Wolach B, Gallin JI. 2010. Hematologically important mutations: X-linked chronic granulomatous disease (third update). Blood Cells Mol. Dis. 45: 246–265. PubMed ID: 20729109
  • 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.

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

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ORDER OPTIONS

View Ordering Instructions

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.

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