TY - JOUR
T1 - Whole-Exome Sequencing Enables Rapid Determination of Xeroderma Pigmentosum Molecular Etiology
AU - Ortega-Recalde, Oscar
AU - Vergara, Jéssica Inés
AU - Fonseca, Dora Janeth
AU - Ríos, Xiomara
AU - Mosquera, Hernando
AU - Bermúdez, Olga María
AU - Medina, Claudia Liliana
AU - Vargas, Clara Inés
AU - Pallares, Argemiro Enrique
AU - Restrepo, Carlos Martín
AU - Laissue, Paul
PY - 2013/6/3
Y1 - 2013/6/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878654795&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0064692
DO - 10.1371/journal.pone.0064692
M3 - Artículo Científico
C2 - 23755135
AN - SCOPUS:84878654795
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e64692
ER -
