title: Whole-exome sequencing enables rapid determination of xeroderma pigmentosum molecular etiology.
abstract: 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.
authors.affiliation: Unidad de Genética, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.
authors.forename: Oscar
authors.initials: O
authors.lastname: Ortega-Recalde
authors.forename: Jéssica Inés
authors.initials: JI
authors.lastname: Vergara
authors.forename: Dora Janeth
authors.initials: DJ
authors.lastname: Fonseca
authors.forename: Xiomara
authors.initials: X
authors.lastname: Ríos
authors.forename: Hernando
authors.initials: H
authors.lastname: Mosquera
authors.forename: Olga María
authors.initials: OM
authors.lastname: Bermúdez
authors.forename: Claudia Liliana
authors.initials: CL
authors.lastname: Medina
authors.forename: Clara Inés
authors.initials: CI
authors.lastname: Vargas
authors.forename: Argemiro Enrique
authors.initials: AE
authors.lastname: Pallares
authors.forename: Carlos Martín
authors.initials: CM
authors.lastname: Restrepo
authors.forename: Paul
authors.initials: P
authors.lastname: Laissue
mesh_terms: D000328:Adult; D059472:Exome / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D010375:Pedigree; D014983:Xeroderma Pigmentosum / Q000235:genetics*; D055815:Young Adult