Which gene is commonly mutated in X-linked agammaglobulinemia?

Which gene is commonly mutated in X-linked agammaglobulinemia?

• A. BTK
• B. AIRE
• C. NFKB2
• D. CD40L

Answer: (A)

Mutations in a gene encoding a B cell signaling kinase disrupt B cell maturation. In X-linked agammaglobulinemia, the defect is in Bruton's tyrosine kinase (BTK), a cytoplasmic tyrosine kinase essential for signaling through the B cell receptor. Without functional BTK, B cells cannot progress from the pre‑B stage to mature B cells in the bone marrow, so there are very few CD19+ B cells and extremely low levels of all immunoglobulin isotypes. This leaves affected individuals susceptible to recurrent bacterial infections early in life and is typically seen in males due to the X‑linked inheritance. Other genes listed correspond to different immunodeficiencies: AIRE mutations cause autoimmune polyglandular syndromes; NFKB2 mutations can lead to CVID‑like hypogammaglobulinemia; CD40L mutations cause Hyper-IgM syndrome with defective class switching.

Mutations in a gene encoding a B cell signaling kinase disrupt B cell maturation. In X-linked agammaglobulinemia, the defect is in Bruton's tyrosine kinase (BTK), a cytoplasmic tyrosine kinase essential for signaling through the B cell receptor. Without functional BTK, B cells cannot progress from the pre‑B stage to mature B cells in the bone marrow, so there are very few CD19+ B cells and extremely low levels of all immunoglobulin isotypes. This leaves affected individuals susceptible to recurrent bacterial infections early in life and is typically seen in males due to the X‑linked inheritance.

Other genes listed correspond to different immunodeficiencies: AIRE mutations cause autoimmune polyglandular syndromes; NFKB2 mutations can lead to CVID‑like hypogammaglobulinemia; CD40L mutations cause Hyper-IgM syndrome with defective class switching.