Abstract
Autosomal recessive hyper-immunoglobulin E syndrome (AR-HIES) caused by DOCK8 defects is characterized by recurrent elevated serum IgE level, elevated peripheral eosinophil count, severe atopy, recurrent viral and bacterial infections, and early-onset malignancy. The clinical, genetic, and immunologic characteristics of DOCK8 mutations in Chinese patients have not been characterized in detail. In this research, we screened seven Chinese candidate patients for mutations within the DOCK8 gene and identified three large novel homozygous deletions and four novel point mutations by targeted deep sequencing. The homozygous deletions displayed autosomal recessive inheritance, and the point mutations were sporadic. Absence of DOCK8 protein was confirmed using flow cytometry and western blotting. Besides the typical clinical features and immunologic impairments of DIDS, proliferation of lymphocytes, cytotoxic function of NK cells, and expression of IL-10 in regulatory B cells were severely impaired in DOCK8 mutant patients which may be associated with abnormal immune responses in DIDS. These findings will contribute to the early diagnosis and treatment of DOCK8 patients.