Clinical and genetic characteristics of xeroderma pigmentosum in Nepal.
J Eur Acad Dermatol Venereol
; 32(5): 832-839, 2018 May.
Article
en En
| MEDLINE
| ID: mdl-29178624
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
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Xerodermia Pigmentosa
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Carcinoma Basocelular
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Carcinoma de Células Escamosas
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Proteínas de Unión al ADN
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Neoplasias del Ojo
/
Neoplasias Primarias Múltiples
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
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Child
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Child, preschool
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Female
/
Humans
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Infant
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Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Eur Acad Dermatol Venereol
Asunto de la revista:
DERMATOLOGIA
/
DOENCAS SEXUALMENTE TRANSMISSIVEIS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia