What is the molecular defect found in WHIM syndrome?

WHIM syndrome, which stands for warts, hypogammaglobulinemia, infections, and myelokathexis, is primarily associated with a molecular defect in the CXCR4 gene. This gene encodes a chemokine receptor that plays a crucial role in the migration and retention of immune cells, particularly in the bone marrow and peripheral tissues.

In WHIM syndrome, mutations in the CXCR4 gene lead to impaired leukocyte trafficking. This results in a reduced ability of neutrophils to exit the bone marrow efficiently, causing an accumulation of these cells in the marrow and a deficit in their numbers in the circulation. This defect contributes to the immunodeficiency and increased susceptibility to infections seen in patients with WHIM syndrome.

The other options pertain to different immunological disorders or functions. For instance, defects in CD40L are associated with hyper-IgM syndrome, while RAG1 mutations are related to severe combined immunodeficiency. IL-2R defects can give rise to immunodeficiencies as well, but none pertain to the clinical features or molecular basis of WHIM syndrome as specifically as the CXCR4 mutation does. Thus, the correct identification of CXCR4 as the defect