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USMLE® Step 1 Question of the Day: Sunlight sensitivity

Osmosis Team
Published on May 8, 2024. Updated on May 8, 2024.

Prepare for USMLE Step 1 with this case! Learn about xeroderma pigmentosum, a rare genetic disorder causing extreme sensitivity to sunlight and increased risk of skin cancer due to defective DNA repair mechanisms. Understand its clinical manifestations, including pigmented skin changes, ocular damage, and neurological complications, for accurate diagnosis and management.

A 4-year-old boy is brought to the office by his parent because of increased sensitivity to sunlight. His parent reports that the patient sunburns easily since birth, even with minimal sun exposure. He has been meeting all developmental milestones and just recently started riding his tricycle with no assistance. Family history is significant for cutaneous squamous cell carcinoma in his paternal grandfather.  Vitals are within normal limits for age. Physical examination shows bilateral conjunctival injection and dryness of the facial skin with rough texture and erythematous macules and freckles. A complete neurological examination shows no abnormalities. Which of the following processes of DNA repair is most likely to be defective in this patient? 

A. DNA mismatch repair 

B. Nonhomologous end joining repair 

C. Homologous recombination 

D. Nucleotide excision repair

E. Base excision repair 

Scroll down for the correct answer!

The correct answer to today's USMLE® Step 1 Question is...

D. Nucleotide excision repair

Before we get to the Main Explanation, let's look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!

Incorrect answer explanations

A. DNA mismatch repair

Incorrect: Defective DNA mismatch repair results in Lynch syndrome (hereditary nonpolyposis colorectal cancer), which is an autosomal dominant genetic disorder that is strongly associated with colorectal cancer. Most patients are asymptomatic, but gastrointestinal bleeding and abdominal pain are the usual presentation. This patient’s history of photosensitivity makes this disorder unlikely.

B. Nonhomologous end joining repair

Incorrect: Nonhomologous end joining refers to joining the ends of DNA fragments to repair the double-stranded breaks. Failure of this repair mechanism is usually observed in ataxia-telangiectasia, due to an abnormal ATM gene. The condition usually manifests in children as cerebellar ataxia, spider angiomas and recurrent infections. Dry skin and photosensitivity is atypical.

C. Homologous recombination 

Incorrect: Homologous recombination refers to repair of damaged DNA using a complementary DNA strand from intact homologous double-stranded DNA. Failure of this mechanism results in Fanconi anemia, which presents with short stature, café-au-lait spots, and thumb/radial defects. Dry pigmented skin with increased sensitivity to sunlight is not seen.

E. Base excision repair 

Incorrect: Base excision repair plays an important role in the repair of spontaneous or toxic deamination (removal of amino groups from nitrogen bases) that results from chemicals like nitrites or nitrosamine. A defect in base excision repair can increase the risk of developing colorectal cancer but is not associated with xeroderma pigmentosum.  

Main Explanation

This patient’s presentation with photosensitive skin since infancy, in combination with physical examination findings of dry and erythematous facial skin with freckles and bilateral conjunctivitis, is strongly suggestive of xeroderma pigmentosum (XP). 

Normally, harmful ultraviolet (UV) radiation creates pyrimidine dimers commonly between two adjacent thymines on one of the DNA strands, distorting the DNA strand in that region of the molecule. Nucleotide excision repair fixes this damage in a stepwise manner as follows: 

  1. Initially, endonucleases make two incisions in the DNA strand on the 3’ side and 5’ side of the damaged bases, leaving a fragment of 12 to 24 nucleotides with free ends, exposing them to exonucleases. 

  2. Exonucleases remove these damaged nucleotides. 

  3. DNA polymerase inserts new nucleotides, and 

  4. DNA ligase seals the bonds once again 

nucleotide excision repair

XP is a rare autosomal recessive disorder that results from mutations in the genes that are involved in nucleotide excision repair. It primarily manifests in childhood with pigmented skin changes (e.g. freckling), skin atrophy, dryness, telangiectasia, and ocular damage which can present as ectropion, conjunctival injection, and/or corneal scarring. Progressive neurodegeneration is also seen in some cases, and this complication may present with sensorineural hearing loss, intellectual impairment, speech delays, ataxia, and peripheral neuropathy. Strict sun avoidance, protection, and frequent skin examination are appropriate management options. 

Major Takeaway

Xeroderma pigmentosum is an autosomal recessive genetic disorder that results from defective nucleotide excision repair mechanisms. It usually manifests in childhood as pigmentary skin changes, signs of photoaging, and ocular damage. 


  • Farrington, S. M., Tenesa, A., Barnetson, R., Wiltshire, A., Prendergast, J., Porteous, M., ... & Dunlop, M. G. (2005). Germline susceptibility to colorectal cancer due to base-excision repair gene defects. The American Journal of Human Genetics, 77(1), 112-119. 

  • Lee, K. J., Piett, C. G., Andrews, J. F., Mann, E., Nagel, Z. D., & Gassman, N. R. (2019). Defective base excision repair in the response to DNA damaging agents in triple negative breast cancer. PloS one, 14(10). 


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The United States Medical Licensing Examination (USMLE®) is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). Osmosis is not affiliated with NBME nor FSMB.