Novel pathological genetic variant associated with DOCK8 deficiency: case report with successful hematopoietic stem...

Deficiency of dedicator of cytokinesis 8 (DOCK8) is a combined immunodeficiency characterized by severe atopic dermatitis, recurrent infections, and elevated serum immunoglobulin E (IgE) levels. Following genetic confirmation, early hematopoietic stem cell transplantation (HSCT) is the treatment of choice. We report a 7-year-old girl who presented with refractory atopic dermatitis and recurrent sinopulmonary infections. Laboratory evaluation revealed markedly elevated total IgE, lymphopenia, decreased memory B cells, and poor vaccine responses. Whole exome sequencing identified a previously unreported homozygous nonsense mutation in the DOCK8 gene (c.5382C>A; p.Tyr1794*). Functional validation was achieved through flow cytometry, which demonstrated significantly reduced DOCK8 protein expression. The patient underwent successful HSCT from a fully matched (10/10) HLA-compatible donor following conditioning with fludarabine and treosulfan. At 1 year follow-up, full donor chimerism was achieved, and the patient remained in remission. This case highlights a novel pathogenic variant in DOCK8 deficiency and demonstrates curative success following definitive diagnosis and timely HSCT.