A 28-year-old man with X-linked agammaglobulinemia presents with recurrent sinopulmonary infections. Flow cytometry of peripheral blood shows absent mature B cells. The molecular defect responsible for the arrest in B-cell development at the pro-B cell to pre-B cell transition is a mutation in:
- A Bruton's tyrosine kinase (BTK) gene on Xq22 ✓
- B CD40 ligand (CD154) gene on Xq26
- C Common gamma chain (γc) gene on Xq13
- D RAG-1 gene on chromosome 11p13
Correct answer: A. Bruton's tyrosine kinase (BTK) gene on Xq22
Explanation
X-linked agammaglobulinemia (XLA) is caused by loss-of-function mutations in the BTK gene at Xq22. BTK is a cytoplasmic tyrosine kinase essential for pre-B cell receptor signaling; without it, B-cell development arrests at the pro-B to pre-B transition, resulting in profound hypogammaglobulinemia. CD40 ligand mutations cause Hyper-IgM syndrome; γc mutations cause SCID with absent T and NK cells; RAG-1 mutations cause autosomal recessive SCID with absent T and B cells.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.