Which disorder involves a mutation affecting the CD40 ligand, resulting in a distinctive immunodeficiency?

Hyper-IgM syndrome is characterized by a mutation in the gene coding for the CD40 ligand (CD40L). This condition is associated with impaired class switching of immunoglobulins, leading to an overproduction of immunoglobulin M (IgM) and a deficiency in other antibody isotypes such as IgG, IgA, and IgE. The CD40-CD40L interaction is crucial for T-cell help in the activation of B-cells and the subsequent production of various immunoglobulin classes. As a result, individuals with Hyper-IgM syndrome have a heightened susceptibility to infections due to the inadequate antibody response.

In contrast, the other disorders listed have different underlying mechanisms and are not primarily associated with mutations in the CD40 ligand. DiGeorge syndrome is primarily due to a deletion on chromosome 22, leading to thymic hypoplasia and various immunological deficiencies. Wiskott-Aldrich syndrome is linked to mutations in the WAS gene, which affects both T-cell and B-cell function, leading to eczema, thrombocytopenia, and recurrent infections. Severe Combined Immunodeficiency (SCID) encompasses several genetic defects that cause severe impairment of both T- and B-lymphocyte functionality.

Thus, the