A 7-year-old girl with recurrent sinopulmonary infections is found to have IgA deficiency, truncal ataxia, and multiple telangiectasias over the bulbar conjunctivae. Serum alpha-fetoprotein is markedly elevated. The gene mutated in this condition encodes a protein that normally functions in:

• A Detection and repair signaling of DNA double-strand breaks ✓
• B V(D)J recombination in developing lymphocytes
• C Class switching via CD40 ligand interaction
• D Purine salvage in lymphocyte metabolism

Explanation

Ataxia-telangiectasia is caused by mutation of the ATM gene, whose product is a serine-threonine kinase that senses DNA double-strand breaks and coordinates repair checkpoints. Defective repair explains chromosomal instability, radiosensitivity, and the elevated AFP. The immunodeficiency features low IgA and IgG2 with recurrent sinopulmonary infections. Adenosine deaminase deficiency causes autosomal recessive SCID, and CD40L defects cause hyper-IgM syndrome.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.