A novel CD40LG deletion causes the hyper-IgM syndrome with normal CD40L expression in a 6-month-old child.

The X-linked hyper-IgM syndrome (XHIGM) is the most common form of HIGM. Patients are clinically diagnosed on the basis of recurrent sinopulmonary infections, accompanied with low levels of IgG and IgA, normal to elevated levels of IgM, and the presence of peripheral B cells. Here, we have reported a novel deletion of four nucleotides in CD40LG exon 3, c.375_378delCAAA, which led to a frameshift mutation with a premature stop codon, p.Asn101*126. The deletion resulted in a truncated protein, in which majority of the extracellular domain was lost. However, detection of surface CD40L was still possible as the intracellular, transmembrane, and part of the extracellular domains were not affected. This indicated that this mutation did not affect protein stability and that immunodetection of CD40L expression is not enough for the diagnosis of XHIGM. Our study strongly suggests that genetic diagnosis for XHIGM should always be performed when clinical data support this diagnosis and CD40L protein is present.