Test Catalog

Test Id : DOCK8

Dedicator of Cytokinesis 8 (DOCK8) Deficiency, Blood

Useful For
Suggests clinical disorders or settings where the test may be helpful

Aids in the diagnosis of dedicator of cytokinesis 8 (DOCK8) deficiency

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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 pathogenic missense variant (point mutation) or a small insertion/deletion (indel)

-Compound heterozygous pathogenic missense variants plus small insertions/deletions

 

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, NK 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 pathogenic alteration in DOCK8 at the protein level; to examine a reported variant of undetermined significance (VUS); 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
A short description of the method used to perform the test

Flow Cytometry

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

DOCK8 Deficiency, B

Aliases
Lists additional common names for a test, as an aid in searching

DOCK8 Deficiency

DOCK8

Dedicator of Cytokinesis 8

Specimen Type
Describes the specimen type validated for testing

Whole Blood EDTA

Ordering Guidance

This flow cytometry test is complementary to genetic testing.

Shipping Instructions

Specimens are required to be received in the laboratory weekdays and by 4 p.m. on Friday. 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 physician name and phone number are required.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions: Send specimen in original tube. Do not aliquot.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Whole Blood EDTA Ambient (preferred) 48 hours PURPLE OR PINK TOP/EDTA

Useful For
Suggests clinical disorders or settings where the test may be helpful

Aids in the diagnosis of dedicator of cytokinesis 8 (DOCK8) deficiency

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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 pathogenic missense variant (point mutation) or a small insertion/deletion (indel)

-Compound heterozygous pathogenic missense variants plus small insertions/deletions

 

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.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

The appropriate reference values will be provided on the report.

Interpretation
Provides information to assist in interpretation of the test results

The results will be reported as the percentage of dedicator of cytokinesis 8 (DOCK8) expression on T cells, B cells, 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
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test cannot be relied upon for identifying carrier status for Dedicator of Cytokinesis 8 (DOCK8) deficiency.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

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; 124:1289-302 e4

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;133:1667-1675

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;134:221-223

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;136:402-412

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; 287:9-19

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; 7:848-855

Method Description
Describes how the test is performed and provides a method-specific reference

The dedicator of cytokinesis 8 (DOCK8) protein expression assay is performed on whole blood. Samples are fixed, permeabilized and stained with antibodies specific for CD45, CD14, CD19, CD3, and CD56 along with either the DOCK8 antibody (unconjugated) or isotype control (unconjugated). A secondary mouse anti-rabbit reporter antibody is added to allow the assessment of DOCK8 and isotype control expression. Samples are then analyzed on a flow cytometer. DOCK8 expression is evaluated on the following populations: T-cells: (CD45+CD14[neg]CD3+), B-cells: (CD45+CD14[neg]CD3[neg]CD19+), NK-cells (CD45+CD14[neg]CD3[neg]CD56+), Monocytes (CD45+CD14+).(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 4 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

4 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

86356 x 4

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports