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  • Test code: 08160
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Phagocyte Defects Panel

Test description

This test analyzes up to 27 genes that are associated with hereditary phagocyte defects (HPD). Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations.

If the patient has undergone a bone marrow transplant prior to genetic testing testing a sample type not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle, but deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Specimen Requirements page for more details.

Note: The NCF1 gene is not offered in this panel.

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Primary panel (27 genes)

CEBPE CLPB CSF2RA CSF3R CTSC CYBA CYBB ELANE FERMT3 FPR1 G6PC3 G6PD GFI1 HAX1 ITGB2 JAGN1 LAMTOR2 NCF2 NCF4 PMM2 SLC35C1 SLC37A4 SPINK5 TAZ VPS13B VPS45 WAS

Hereditary phagocyte defects (HPD) including:



Gene Disorder Protein name Protein symbol
CEBPE Specific granule deficiency C/EBP-epsilon C/EBP
CLPB 3-Methylglutaconic aciduria caseinolytic peptidase B CLPB
CSF2RA Pulmonary alveolar proteinosis granulocyte/macrophage colony-stimulating factor GMCSF
CSF3R G-CSF receptor deficiency granulocyte colony-stimulating factor receptor CSF3R
CTSC Papillon-Lefèvre Syndrome cathepsin C CTSC
CYBA Autosomal recessive CGD 22kD-phagocyte oxidase p22-phox
CYBB X-linked CGD 91kD-phagocyte oxidase p91-phox
ELANE Elastase deficiency (SCN1), cyclic neutropenia elastase ELANE
FERMT3 Leukocyte adhesion deficiency type 3 KINDLIN3 KINDLIN3
FPR1 Localized juvenile periodontitis Formylated peptide receptor FPR1
G6PC3 G6PC3 deficiency (SCN4) glucose-6-phosphatase beta G6PC3
G6PD Neutrophil G6PD deficiency glucose-6-phosphate dehydrogenase G6PD
GFI1 GFI 1 deficiency (SCN2) growth factor-independent 1 GFI1
HAX1 Kostmann Disease (SCN3) HCLS1-associated protein X1 HAX1
ITGB2 Leukocyte adhesion deficiency type 1 integrin beta 2 ITGB2
JAGN1 JAGN1 deficiency homolog of drosophila jagunal 1 JAGN1
LAMTOR2 P14/LAMTOR2 deficiency p14 P14
NCF2 Autosomal recessive CGD 67kD-phagocyte oxidase p67-phox
NCF4 Autosomal recessive CGD 40kD-phagocyte oxidase p40-phox
PMM2 PMM2-congenital disorder of glycosylation (CDG-Ia) Phosphomannomutase PMM2
SLC35C1 Leukocyte adhesion deficiency type 2 GDP-fucose transporter 1 SLC35C1
SLC37A4 Glycogen storage disease type 1b glucose-6-phosphate transporter 1 G6PT1
SPINK5 Comel-Netherton syndrome lymphoepithelial kazal type related inhibitor LEKT1
TAZ Barth syndrome tafazzin TAZ
VPS13B Cohen syndrome vacuolar protein sorting 13 homolog B COH1
VPS45 VPS45 deficiency (SCN5) vaculolar protein sorting 45 VPS45
WAS Wiskott-Aldrich syndrome, X-linked neutropenia/ myelodysplasia WAS protein WASP

Phagocytes are the body’s first defense against invading microorganisms. Hereditary genetic changes that affect the number and function of phagocytes can increase the risk for life threatening bacterial and fungal infections, mainly of the soft tissues. Most phagocytic disorders can be broken down into three main types: chronic granulomatous disease, congenital phagocyte defects and leukocyte adhesion deficiency. While most symptoms of HPD appear during the first year of life, some individuals can have later age of onset. Approximately 8% of primary immunodeficiencies are the result of a phagocytic disorder. Penetrance is complete for most types of HPD.

Determination of an underlying genetic predisposition in an individual with a personal or family history of HPD is critical for the selection of therapy regimens, consideration of bone marrow or stem cell transplant, and counseling of the individual and their family.

The following genes confer an increased risk of HPD in:

  • an autosomal dominant inheritance pattern – ELANE, FPR1, GFI1
  • an autosomal recessive inheritance pattern – CEBPE, CLPB, CTSC, CYBA, FERMT3, G6PC3, HAX1, ITGB2, JAGN1, LAMTOR2, NCF2, NCF4, PMM2, SLC35C1, SLC37A4, SPINK5, VPS13B, VPS45
  • an autosomal dominant or autosomal recessive inheritance pattern – CSF3R
  • an X-linked inheritance pattern – CYBB, G6PD, TAZ, WAS
  • CSF2RA is found on the pseudoautosomal region on the X and Y chromosomes. Biallelic pathogenic variants cause disease

This panel may be considered for individuals whose personal and/or family history is suggestive of a hereditary predisposition to phagocyte defects, including any of the following:

  • chronic common bacterial and fungal infections
  • unusual bacterial and fungal infections
  • omphalitis in infants
  • congenital neutropenia
  • a family history of HPD

If the patient has undergone a bone marrow transplant prior to genetic testing testing a sample type not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle, but deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Specimen Requirements for more details.

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  2. Wortmann, SB, et al. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. Am. J. Hum. Genet. 2015; 96(2):245-57. PMID: 25597510
  3. Saunders, C, et al. CLPB variants associated with autosomal-recessive mitochondrial disorder with cataract, neutropenia, epilepsy, and methylglutaconic aciduria. Am. J. Hum. Genet. 2015; 96(2):258-65. PMID: 25597511
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  29. Angelini, R, et al. Cardiolipin fingerprinting of leukocytes by MALDI-TOF/MS as a screening tool for Barth syndrome. J. Lipid Res. 2015; 56(9):1787-94. PMID: 26144817
  30. Roberts, AE, et al. The Barth Syndrome Registry: distinguishing disease characteristics and growth data from a longitudinal study. Am. J. Med. Genet. A. 2012; 158A(11):2726-32. PMID: 23045169
  31. Vilboux, T, et al. A congenital neutrophil defect syndrome associated with mutations in VPS45. N. Engl. J. Med. 2013; 369(1):54-65. PMID: 23738510
  32. Stepensky, P, et al. The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy. Blood. 2013; 121(25):5078-87. PMID: 23599270
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  38. Madkaikar, M, et al. Molecular characterization of leukocyte adhesion deficiency-I in Indian patients: identification of 9 novel mutations. Blood Cells Mol. Dis. 2015; 54(3):217-23. PMID: 25703682
  39. Kuijpers, TW, et al. LAD-1/variant syndrome is caused by mutations in FERMT3. Blood. 2009; 113(19):4740-6. PMID: 19064721
  40. Malinin, NL, et al. A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. Nat. Med. 2009; 15(3):313-8. PMID: 19234460
  41. Hidalgo, A, et al. Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene. Blood. 2003; 101(5):1705-12. PMID: 12406889
  42. Helmus, Y, et al. Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter. Blood. 2006; 107(10):3959-66. PMID: 16455955
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  49. Bustamante, J, et al. Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease. Nat. Immunol. 2011; 12(3):213-21. PMID: 21278736
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Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CEBPE NM_001805.3
CLPB NM_030813.5
CSF2RA* NM_006140.4
CSF3R NM_000760.3
CTSC NM_001814.5
CYBA NM_000101.3
CYBB NM_000397.3
ELANE NM_001972.2
FERMT3 NM_031471.5
FPR1 NM_002029.3
G6PC3 NM_138387.3
G6PD NM_001042351.2
GFI1 NM_005263.3
HAX1 NM_006118.3
ITGB2 NM_000211.4
JAGN1 NM_032492.3
LAMTOR2 NM_014017.3
NCF2 NM_000433.3
NCF4 NM_013416.3
PMM2 NM_000303.2
SLC35C1 NM_018389.4
SLC37A4 NM_001164277.1
SPINK5 NM_006846.3
TAZ NM_000116.4
VPS13B NM_017890.4
VPS45 NM_007259.4
WAS NM_000377.2

CSF2RA: Deletion/duplication analysis is not offered for this gene.