Clinical and genetic characteristics of xeroderma pigmentosum in Nepal

Autor: Nadem Soufir, V. Grybek, A.-S. Lebre, Florent Grange, P. Espi, S. Parajuli, T. Grange, M. Benfodda, Udaya Raj Paudel, A. Grange
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Oncology
Skin Neoplasms
DNA Mutational Analysis
Pilot Projects
medicine.disease_cause
Neoplasms
Multiple Primary
030207 dermatology & venereal diseases
0302 clinical medicine
Missense mutation
Prospective Studies
Child
Mutation
Melanoma
Homozygote
High-Throughput Nucleotide Sequencing
Xeroderma Pigmentosum Group A Protein
DNA-Binding Proteins
Keratosis
Actinic
Phenotype
Infectious Diseases
Child
Preschool
Carcinoma
Squamous Cell
Female
Receptor
Melanocortin
Type 1
Adult
Heterozygote
medicine.medical_specialty
Xeroderma pigmentosum
Adolescent
Dermatology
Eye neoplasm
Young Adult
03 medical and health sciences
Nepal
Internal medicine
medicine
Humans
Xeroderma Pigmentosum Group D Protein
Xeroderma Pigmentosum
business.industry
Eye Neoplasms
Infant
medicine.disease
030104 developmental biology
Carcinoma
Basal Cell
ERCC2
Skin cancer
business
Founder effect
Zdroj: Journal of the European Academy of Dermatology and Venereology. 32:832-839
ISSN: 0926-9959
Popis: 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.
Databáze: OpenAIRE
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