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HelpTest Code DOCK8 Dedicator of Cytokinesis 8 (DOCK8) Deficiency, Blood
Ordering Guidance
This flow cytometry test is complementary to genetic testing.
Shipping Instructions
Testing is performed Monday through Friday. Specimens not received by 4 p.m. (CST) on Friday may be canceled.
Collect and package specimen as close to shipping time as possible. It is recommended that specimens arrive within 24 hours of collection.
Samples arriving on the weekend and observed holidays may be canceled.
Necessary Information
Ordering healthcare professional name and phone number are required.
Specimen Required
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.
Useful For
Aiding in the diagnosis of dedicator of cytokinesis 8 (DOCK8) deficiency
This test is not useful for assessing DOCK8 carrier status.
Genetics Test Information
The human DOCK8 gene is on chromosome 9.
Autosomal recessive germline pathogenic variants observed in dedicator of cytokinesis 8 (DOCK8) deficiency fall into the following main categories:
-Large homozygous deletions
-Compound heterozygous large deletion plus disease-causing missense variant (point alteration) or a small deletion/insertion (delin)
-Compound heterozygous disease-causing missense variants plus small deletions/insertions
A study of 34 patients with DOCK8 deficiency has shown variable degrees of somatic reversion in half of the cohort, mainly in memory T cells and NK cells. The extent of somatic reversion is inversely correlated with cumulative disease burden. This type of repair cannot happen in cases with large homozygous deletions.
Highlights
The test detects the expression of dedicator of cytokinesis 8 (DOCK8) in T cells, B cells, natural killer cells, and monocytes in the peripheral blood.
It can be used as a screening step prior to genetic testing for DOCK8; to confirm the finding of an established disease-causing alteration in DOCK8 at the protein level; to examine a reported variant of undetermined significance; and to evaluate the potential presence of somatic reversion in a patient with DOCK8 deficiency.
It can help distinguish DOCK8 deficiency from conditions with overlapping clinical manifestations, including Job syndrome (AD-HIES), ZNF341 deficiency, and severe atopic dermatitis.
Method Name
Flow Cytometry
Reporting Name
DOCK8 Deficiency, BSpecimen Type
Whole Blood EDTASpecimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Whole Blood EDTA | Ambient | 48 hours | PURPLE OR PINK TOP/EDTA |
Reject Due To
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | OK |
Clinical Information
Dedicator of cytokinesis 8 (DOCK8) is an atypical guanine exchange factor that plays a role in regulating actin polymerization and cytoskeletal rearrangement. DOCK8 is important in both innate and adaptive immunity by contributing to cellular migration, cytotoxicity, antibody production, and immunological memory.
DOCK8 deficiency is a rare, combined immunodeficiency with an autosomal recessive inheritance that typically presents in childhood. Its clinical features include atopic disease, recurrent sinopulmonary infections, cutaneous viral infection, Staphylococcus aureus skin infections, and cancer.
DOCK8 deficiency is diagnosed based on clinical phenotype, immunologic findings, and molecular analysis.
Diseases in the differential diagnosis include Job syndrome (AD-HIES), ZNF341 deficiency, and severe atopic dermatitis.
Assessment of DOCK8 expression on immune cells is an important component and facilitates the diagnosis of this condition and the timely treatment of the patient.
Reference Values
The appropriate reference values will be provided on the report.
Interpretation
The results will be reported as the percentage of dedicator of cytokinesis 8 (DOCK8) expression on T cells, B cells, natural killer (NK) cells, and monocytes.
The absence of DOCK8 expression on all cell types will be consistent with DOCK8 deficiency. In this case, genetic analysis of DOCK8 to confirm the diagnosis and to identify the underlying alteration will be recommended.
The expression of DOCK8 on a subset of T cells and/or NK cells could suggest somatic reversion in a patient with DOCK8 deficiency, which can modulate disease phenotype over time.
Cautions
This test cannot be relied upon for identifying carrier status for dedicator of cytokinesis 8 deficiency.
Clinical Reference
1. Engelhardt KR, McGhee S, Winkler S, et al. Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. J Allergy Clin Immunol. 2009; 124(6):1289-302 e4. doi:10.1016/j.jaci.2009.10.038
2. Jing H, Zhang Q, Zhang Y, et al. Somatic reversion in dedicator of cytokinesis 8 immunodeficiency modulates disease phenotype. J Allergy Clin Immunol. 2014;133(6):1667-1675. doi:10.1016/j.jaci.2014.03.025
3. Pai SY, de Boer H, Massaad MJ, et al. Flow cytometry diagnosis of dedicator of cytokinesis 8 (DOCK8) deficiency. J Allergy Clin Immunol. 2014;134(1):221-223. doi:10.1016/j.jaci.2014.02.023
4. Engelhardt KR, Gertz ME, Keles S, et al. The extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency. J Allergy Clin Immunol. 2015;136(2):402-412. doi:10.1016/j.jaci.2014.12.1945
5. Su HC, Jing H, Angelus P, Freeman AF. Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome. Immunol Rev. 2019;287(1):9-19. doi:10.1111/imr.12723
6. Aydin SE, Freeman AF, Al-Herz W, et al. Hematopoietic stem cell transplantation as treatment for patients with DOCK8 deficiency. J Allergy Clin Immunol Pract. 2019;7(3):848-855. doi:10.1016/j.jaip.2018.10.035
Day(s) Performed
Monday through Friday
Report Available
2 to 4 daysSpecimen Retention Time
4 daysPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
86356 x 4
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| DOCK8 | DOCK8 Deficiency, B | 96415-5 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 608496 | %CD3+DOCK8+ | 96416-3 |
| 608497 | %CD19+DOCK8+ | 96417-1 |
| 608498 | %CD56+DOCK8+ | 96418-9 |
| 608499 | %CD14+DOCK8+ | 96419-7 |
| 608513 | DOCK8 Interpretation | 69052-9 |