In Cockayne syndrome, DNA repair is defective specifically for transcription-coupled NER (TC-NER). What is the clinical phenotype compared to classic XP (global-genome NER defect)?

• A Cockayne syndrome: photosensitivity + severe neurodegeneration + no increased skin cancer risk ✓
• B Cockayne syndrome: same phenotype as XP with markedly elevated cancer risk
• C Cockayne syndrome: isolated immunodeficiency without photosensitivity
• D Cockayne syndrome: only premature skin aging, no neurological involvement

Explanation

TC-NER preferentially repairs damage in actively transcribed genes; its deficiency in Cockayne syndrome causes severe neurodegeneration (progressive cognitive decline, microcephaly, 'bird-like facies') and photosensitivity but, paradoxically, does NOT increase cancer risk significantly. This is because while transcribed genes are repaired less efficiently, the untranscribed genome undergoes normal apoptosis when damaged. Classic XP (GG-NER defect) shows extreme UV-induced skin cancers but less neurodegeneration. CS demonstrates that cancer prevention and DNA repair are partially separable.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.