Abstract: Objective To explore the clinical and genetic features of hyper-IgE syndrome with recurrent infection caused by DOCK8 gene variation. Methods The clinical data of hyper-IgE syndrome in 2 children were analyzed retrospectively, including whole exome sequencing, Sanger verification of pathogenic site, and the expression level of DOCK8 gene in peripheral blood. Results Both children, 1 boy and 1 girl aged 5 years 2 months and 4 years 8 months respectively, were visited for recurrent infection, persistent rash or pustules. The children had no special facial features. The serum IgE level was significantly increased, and the eosinophils in peripheral blood were significantly increased. There were compound heterozygous variants of IVS2+1G>A and c.1729G>A (p.A577T) in DOCK8 gene of the girl, which came from her parents respectively. The DOCK8 gene of the boy had compound heterozygous variation of paternal C.2248G>A (p.E750K) and maternal C.1685T>G (p.L562R). Bioinformatics analysis showed that the three missense variants of p. A 577T, p.E 750K and p.L 562R were conserved among different species. The results of real-time PCR showed that the expression level of DOCK8 gene in peripheral blood of the girl decreased significantly. Conclusion DOCK8 gene variation is a common cause of hyper-IgE syndrome with recurrent infection, which expands the DOCK8 gene variation spectrum.

Key words: hyper-IgE syndrome; DOCK 8 gene; clinical phenotype; variation