Somatic reversion in dedicator of cytokinesis 8 immunodeficiency modulates disease phenotype.

ABSTRACT:

Background

Autosomal recessive loss-of-function mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency characterized by atopy, recurrent infections, and cancer susceptibility. A genotype-phenotype explanation for the variable disease expression is lacking.

Objective

We investigated whether reversions contributed to the variable disease expression.

Methods

Patients followed at the National Institutes of Health's Clinical Center were studied. We performed detailed genetic analyses and intracellular flow cytometry to detect DOCK8 protein expression within lymphocyte subsets.

Results

We identified 17 of 34 DOCK8-deficient patients who had germline mutations with variable degrees of reversion caused by somatic repair. Somatic repair of the

SUBMITTER: Jing H 

PROVIDER: S-EPMC4132167 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature