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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.

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