A novel CD40LG mutation causing X‑linked hyper-IgM syndrome

X-linked hyper-IgM (X-HIGM), which results from mutations of the CD40 ligand gene (CD40LG) located on chromosome Xq26.3, is characterized by a defective T-B lymphocyte cross talk and class switch recombination (CSR). The present study aimed to evaluate the expression of CD40L and lymphocyte subsets using flow cytometry and to identify the novel genetic defect of <i>CD40LG</i> responsible for X-HIGM in a Chinese family. We reported an X-HIGM case caused by a novel mutation in CD40LG. The expression of CD40L was absent on the surface of activated CD4 + T cells evaluated using flow cytometry. The total number of mature B cells in circulation was normal, but memory B cells were significantly decreased. In helper T cells, Th2 was dominant, and the numbers of Th1 and Th17 were decreased. The results of genetic analysis revealed a new causative mutation in CD40L (NM_000074;exon5;c.505_506del), which leads to a change in amino acids (p.Y169Lfs*31) appearing in the proband. The frame shift mutation led to incorrect amino acid translation and loss of β-pleated sheet and loop region, which produced a mutant dysfunctional protein. This study provides a complete picture of X-HIGM and broadens our knowledge of the pathogenicity of the CD40L variant spectrum.