Novel compound heterozygous mutations of DOCK2 associated with early-onset recurrent infections

Introduction Dedicator of cytokinesis 2 (DOCK2) deficiency is a rare combined immunodeficiency characterized by defects in both cellular and humoral immunity and caused by pathogenic mutations in the DOCK2 gene. Herein, we report a 3-year-8-month-old Chinese girl presenting with recurrent infections, immune thrombocytopenia (ITP), elevated IgE levels, and a hemophagocytic lymphohistiocytosis (HLH)-like episode to broaden the clinical phenotype spectrum of the DOCK2 defect. Methods All tests and molecular genetic analyses were performed after obtaining informed consent from the parents. Demographic, clinical, and laboratory findings were abstracted from outpatient and inpatient encounters. Whole-exome sequencing (WES) was performed on peripheral blood cells to identify the genetic etiology, followed by immunological evaluation (including lymphocyte subset analysis, T-cell receptor Vβ repertoire analysis, and neutrophil oxidative function assays) and in silico prediction. Sanger sequencing was used to confirm the identified variants. Results WES identified two novel compound heterozygous variants in DOCK2 (c. 106 C>T, p.R36X and c. 2150T>C, p.L717P), each inherited from one parent. Immunological evaluation revealed combined immune defects involving T cells and B cells, including reduced T/B cell subsets, skewed TCR repertoire, and impaired T cell proliferation. In silico analyses indicated that the variants affect highly conserved residues and are predicted to disrupt protein structure. The patient received supportive treatment, regular intravenous immunoglobulin replacement therapy, and sulfonamide prophylaxis, resulting in effective disease control. Discussion This case expands the genotypic and phenotypic spectrum of DOCK2 deficiency and highlights its critical role in human immune regulation. It also underscores the importance of early genetic diagnosis to guide timely clinical management. However, functional validation experiments were not performed to further confirm the pathogenicity of the identified variants, and additional protein expression studies are warranted.