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Whole-Exome Sequencing Enables Rapid Determination of Xeroderma Pigmentosum Molecular Etiology

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme sensitivity to actinic pigmentation changes in the skin and increased incidence of skin cancer. In some cases, patients are affected by neurological alterations. XP is caused by mutations in 8 distinct genes (...

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Detalles Bibliográficos
Autores principales: Ortega-Recalde, Oscar, Vergara, Jéssica Inés, Fonseca, Dora Janeth, Ríos, Xiomara, Mosquera, Hernando, Bermúdez, Olga María, Medina, Claudia Liliana, Vargas, Clara Inés, Pallares, Argemiro Enrique, Restrepo, Carlos Martín, Laissue, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670841/
https://www.ncbi.nlm.nih.gov/pubmed/23755135
http://dx.doi.org/10.1371/journal.pone.0064692
Descripción
Sumario:Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme sensitivity to actinic pigmentation changes in the skin and increased incidence of skin cancer. In some cases, patients are affected by neurological alterations. XP is caused by mutations in 8 distinct genes (XPA through XPG and XPV). The XP-V (variant) subtype of the disease results from mutations in a gene (XPV, also named POLH) which encodes for Polη, a member of the Y-DNA polymerase family. Although the presence and severity of skin and neurological dysfunctions differ between XP subtypes, there are overlapping clinical features among subtypes such that the sub-type cannot be deduced from the clinical features. In this study, in order to overcome this drawback, we undertook whole-exome sequencing in two XP sibs and their father. We identified a novel homozygous nonsense mutation (c.897T>G, p.Y299X) in POLH which causes the disease. Our results demonstrate that next generation sequencing is a powerful approach to rapid determination of XP genetic etiology.