A 4-year-old boy with xeroderma pigmentosum (XP) group A develops progressive neurological deterioration. The underlying molecular defect responsible for both the cutaneous and neurological features is:

• A Defective base excision repair of alkylated DNA bases
• B Defective nucleotide excision repair (NER) of UV-induced pyrimidine dimers ✓
• C Inability to replicate past DNA lesions due to absent translesion synthesis
• D Defective mismatch repair causing microsatellite instability

Explanation

Xeroderma pigmentosum is caused by defective nucleotide excision repair (NER) of UV-induced DNA damage, specifically cyclobutane pyrimidine dimers and 6-4 photoproducts. XP-A has a mutation in XPA, which is critical for both global genome NER and transcription-coupled NER. Neurological features (De Sanctis-Cacchione syndrome) arise because neurons cannot repair UV-like oxidative DNA damage. Eight complementation groups are described (XP-A through XP-G, and XP variant). XP-V (variant) has defective translesion synthesis (DNA polymerase eta), spares NER, and has milder neurological features. Mismatch repair defects cause Lynch syndrome; base excision repair defects are not the mechanism in XP.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.