Preferred test to assess common molecular causes of chronic granulomatous disease.
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics of chronic granulomatous disease (CGD):
A primary immunodeficiency disorder characterized by recurrent, severe bacterial and fungal infections of the skin, lymph nodes, liver, lungs, bones, or visceral organs. Dysregulated inflammatory responses result in granulomas.
Incidence: Approximately 1 in 250,000 births.
Inheritance: X-linked recessive for CYBB; de novo mutations in 10-20 percent of affected males. Autosomal recessive for NCF1.
Cause: Pathogenic mutations in the CYBB gene result in X-linked CGD that accounts for 60-70 percent of all CGD. Autosomal recessive CGD may result from mutations in NCF1 (25 percent), CYBA (<5 percent), NCF2 (<5 percent) and NCF4 (very rare).
Clinical Sensitivity: 86 percent for CGD.
Methodology: Polymerase Chain Reaction/High-Resolution Melt Analysis. Identified CYBB sequence variants are confirmed using targeted, bidirectional sequencing.
Analytical Sensitivity: 99 percent for CYBB and homozygous GT deletion, 90 percent for heterozygous GT deletion.
Analytical Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Deep intronic mutations in CYBB, mutations in NCF1 other than the GT deletion in exon 2, and mutations in additional genes associated with CGD, are not evaluated in males or females. Large CYBB gene deletions/duplications will not be detected in females. Breakpoints of large deletions/duplications will not be determined in males. Because of potential recombination between NCF1 and its pseudogenes, the lack of detection of the GT deletion in exon 2 does not rule out carrier status for autosomal recessive CGD.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
|Component Test Code*||Component Chart Name||LOINC|
|2006357||Chronic Granulomatous Disease, Specimen||31208-2|
|2006358||Chronic Granulomatous Disease||48728-0|
|2006359||Chronic Granulomatous Disease, Interpret||50398-7|
- CGD mutation testing
- CYBB x-linked mutations