A 12-year-old boy develops severe blistering sunburns after minimal sun exposure, followed by freckling, poikiloderma, and multiple early skin cancers including basal cell carcinoma and melanoma by adolescence. The underlying defect lies in which pathway?

• A Double-strand break repair via homologous recombination
• B Mismatch repair of replication errors
• C Base excision repair of oxidative damage
• D Nucleotide excision repair of UV-induced DNA damage ✓

Explanation

Xeroderma pigmentosum results from defects in nucleotide excision repair genes (such as XPA through XPG) responsible for removing UV-induced pyrimidine dimers. This causes extreme UV sensitivity, early freckling and poikiloderma, and up to a 10,000-fold increased risk of melanoma and non-melanoma skin cancer in childhood. Mismatch repair defects cause Lynch syndrome instead, eliminating option B.

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.