Abstract: ObjectiveTo investigate the clinical features and genetic variation of WHIM syndrome caused by CXCR4 gene mutation.MethodsThe clinical data and whole exome sequencing results of 3 children with WHIM syndrome caused by mutation of CXCR4 gene were retrospectively analyzed. Systematic search and literature review were conducted to collect patients with WHIM syndrome, and to summarize clinical manifestations and gene mutation information.ResultsThree children with WHIM syndrome were all males. The diagnosis age of 3 patients was 11 years, 13 months and 5 years, respectively. All cases had recurrent infection, 1 case developed diabetes, no patients had developed warts. After the treatment with G-CSF, white blood cells could rise to normal, but were prone to decline. All patients showed lymphopenia and neutropenia, but not periodically. Immunoglobulin decreased in all 3 cases. Gene results of whole exome sequencing showed all of the three patients had the same mutation: C-terminal heterozygous exon 2 of CXCR4 gene, and a base substitution mutation (1000C>T) occurred at the second exon cleavage site of CXCR4 gene. A total of 45 English articles and 1 Chinese literature were retrieved from the database. Altogether with the 3 patients in this study, 74 patients with WHIM syndrome were reported so far.ConclusionWHIM syndrome is a rare autosomal dominant genetic disease. Patients can present with warts, recurrent infection, leukopenia and myelokathexis. WHIM syndrome should be considered when young patients manifest symptoms described above except for the warts, thus gene analysis is critical for the diagnosis of the disease.