Test ID: DOCK8    
Dedicator of Cytokinesis 8 (DOCK8) Deficiency, Blood

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

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.

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.

Flow Cytometry