Preferred test to assess common molecular causes of chronic granulomatous disease.
- Patient Preparation
- Lavender (EDTA), Pink (K2EDTA), Yellow (ACD).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
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 variants in 10-20 percent of affected males. Autosomal recessive for NCF1.
Cause: Pathogenic variants in the X-linked CYBB gene (60-70 percent), pathogenic variants in autosomal recessive genes NCF1 (25 percent), CYBA (Less than 5 percent), NCF2 (Less than 5 percent) and NCF4 (very rare).
Clinical Sensitivity: Up to 78 percent for CGD
Methodology: Bidirectional sequencing of the CYBB coding region and intron-exon boundaries. Polymerase Chain Reaction/High-Resolution Melt Analysis to assess for the common NCF1 c.75_76delGT variant.
Analytical Sensitivity: 99 percent for CYBB and homozygous NCF1 c.75_76delGT deletion, 90 percent for heterozygous NCF1 c.75_76delGT deletion.
Analytical Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region variants, deep intronic variants, and large duplications will not be detected in patients of either sex; large deletions will not be detected in females. Variants in NCF1 other than c.75_76delGT are not evaluated. Because of potential recombination between NCF1 and its pseudogenes, the lack of detection of the c.75_76delGT variant does not rule out carrier status for autosomal recessive CGD.
|Component Test Code*||Component Chart Name||LOINC|
|3000545||CGD PAN Specimen||31208-2|
|3000546||CGD PAN Interpretation||90743-6|
- CGD mutation testing
- CYBB X-Linked mutation