Xeroderma pigmentosum (XP) is an autosomal recessive genodermatosis with markedly increased skin cancer risk. The primary defect is in:

• A Mismatch repair of DNA replication errors
• B Base excision repair of oxidative DNA damage
• C Homologous recombination repair of double-strand breaks
• D Nucleotide excision repair (NER) of UV-induced pyrimidine dimers ✓

Explanation

Xeroderma pigmentosum results from defective nucleotide excision repair (NER), which is the principal pathway for removing UV-induced photoproducts—particularly cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts. Eight XP complementation groups (XPA–XPG and XPV) are identified; XPV (variant) has defective translesion synthesis via DNA polymerase eta rather than NER. Without NER, UV-induced mutations accumulate in proto-oncogenes and tumour suppressor genes, leading to a >1000-fold increased skin cancer risk. Mismatch repair defects cause Lynch syndrome; BER defects do not cause photosensitivity.

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.