Clinical and genetic characteristics of xeroderma pigmentosum in Nepal

J Eur Acad Dermatol Venereol. 2018 May;32(5):832-839. doi: 10.1111/jdv.14717. Epub 2017 Dec 18.


Background: Little is known about xeroderma pigmentosum (XP) in Himalayan countries.

Objective: To describe clinical characteristics of XP in Nepal and investigate its genetic bases.

Methods: This study was carried out on all consecutive patients referred for XP to a Nepalese tertiary referral centre in 2014-2015. Clinical data were collected using a standardized questionnaire. DNA was extracted from salivary samples, and next-generation sequencing (NGS) was conducted using a panel covering all 8 known XP genes (classical XP (XP-A to XP-G) and XP variant) and a skin cancer modifier gene, the melanocortin 1 receptor gene (MC1R).

Results: Seventeen patients (median age: 15 years; range: 1-32) were included. Twelve had skin cancers (including a total of 8 squamous cell carcinomas, 60 basal cell carcinomas, ocular carcinomas requiring an orbital exenteration in 3 patients, but no melanoma). Fifteen patients carried the same homozygous non-sense XPC mutation c.1243C>T, p.R415X. A homozygous non-sense XPA mutation (p.W235X) was found in the only patient with a history of early severe sunburn reaction and associated neurological symptoms. Associated genetic alterations included heterozygous missense variants in XPD/ERCC2 gene and the presence of MC1R variant R163Q in 5 and 9 patients, respectively.

Conclusion: Although not previously reported, XP seems frequent in Nepal. Patients often presented with a very severe phenotype after a long history of excessive sun exposure without knowledge of the disease. Fifteen of 17 had the same p.R415X XPC mutation, which seems very specific of XP in Nepal, suggesting a founder effect. NGS analyses frequently revealed associated genetic alterations which could play a modifier role in the clinical expression of the disease.

MeSH terms

  • Adolescent
  • Adult
  • Carcinoma, Basal Cell / etiology*
  • Carcinoma, Squamous Cell / etiology*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Eye Neoplasms / etiology*
  • Female
  • Heterozygote
  • High-Throughput Nucleotide Sequencing
  • Homozygote
  • Humans
  • Infant
  • Keratosis, Actinic / etiology
  • Male
  • Mutation
  • Neoplasms, Multiple Primary / etiology*
  • Nepal
  • Phenotype
  • Pilot Projects
  • Prospective Studies
  • Receptor, Melanocortin, Type 1 / genetics
  • Skin Neoplasms / etiology*
  • Xeroderma Pigmentosum / complications
  • Xeroderma Pigmentosum / genetics*
  • Xeroderma Pigmentosum Group A Protein / genetics
  • Xeroderma Pigmentosum Group D Protein / genetics
  • Young Adult


  • DNA-Binding Proteins
  • Receptor, Melanocortin, Type 1
  • XPA protein, human
  • Xeroderma Pigmentosum Group A Protein
  • XPC protein, human
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human