A 7-year-old girl has recurrent sinopulmonary infections, progressive truncal and limb ataxia, and dilated conjunctival telangiectasias. Serum IgA is deficient and alpha-fetoprotein is elevated. Chromosome breakage analysis shows increased sensitivity to ionizing radiation. The underlying genetic defect is a mutation in a gene whose normal product functions in:

• A Thymic epithelial development
• B V(D)J recombination of immunoglobulin genes
• C Detection and repair of DNA double-strand breaks ✓
• D Purine salvage in lymphocytes

Explanation

Ataxia-telangiectasia results from ATM gene mutation; ATM encodes a kinase that senses DNA double-strand breaks and coordinates repair checkpoints, explaining radiosensitivity, chromosome instability, and elevated AFP. IgA deficiency with recurrent sinopulmonary infection accompanies the neurologic findings. V(D)J recombination defects cause SCID, thymic developmental failure causes DiGeorge syndrome, and purine salvage defects define ADA deficiency or Lesch-Nyhan.

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.