Mutation of the CD40L Gene in X-Linked Hyper-IgM Syndrome: Two Case Reports in Sibling Chinese Patients and a Literature Review

We report a novel mutation of the CD40L gene in X-linked hyper-IgM syndrome (XHIGM) in two sibling Chinese patients, about which we made a literature review. The two sibling boys were born to un-consanguineous parents and the proband was presented at six months of age with pneumonia, infectious diarrhea, abdominal pain, perianal abscess, anemia, and thrush alternately despite regularly intravenous immunoglobulin and anti-infection treatment. The proband died at age two due to pneumonia and his brother died at one-year-old due to perianal abscess. The proband had a less detectable expression of CD40L on the surface of peripheral blood leucocyte and granulocytes, whereas his mother had a drop of CD40L expression compared to a control group made up of healthy test subjects. Mutation analysis revealed the two sibling patients had a missense mutation within Exon 5 of CD40L gene at nucleotide position 448 (488T>G), which made a valine code (GTT) changing to a glycine code (GGT) at position 168 (V163G) of CD40L protein expression. The same heterozygous form (V163G, T>G) was also found in their mother, but the mother was not sick. There was no similar mutation former found in the father. In summary, it is the first time to report the two sibling Chinese boys of a novel missense mutation (V163G) in exon 5 in the CD40L gene.