<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Chacón-Solano, E</style></author><author><style face="normal" font="default" size="100%">León, C</style></author><author><style face="normal" font="default" size="100%">Díaz, F</style></author><author><style face="normal" font="default" size="100%">García-García, F</style></author><author><style face="normal" font="default" size="100%">García, M</style></author><author><style face="normal" font="default" size="100%">Escámez, M J</style></author><author><style face="normal" font="default" size="100%">Guerrero-Aspizua, S</style></author><author><style face="normal" font="default" size="100%">Conti, C J</style></author><author><style face="normal" font="default" size="100%">Mencía, Á</style></author><author><style face="normal" font="default" size="100%">Martínez-Santamaría, L</style></author><author><style face="normal" font="default" size="100%">Llames, S</style></author><author><style face="normal" font="default" size="100%">Pévida, M</style></author><author><style face="normal" font="default" size="100%">Carbonell-Caballero, J</style></author><author><style face="normal" font="default" size="100%">Puig-Butillé, J A</style></author><author><style face="normal" font="default" size="100%">Maseda, R</style></author><author><style face="normal" font="default" size="100%">Puig, S</style></author><author><style face="normal" font="default" size="100%">de Lucas, R</style></author><author><style face="normal" font="default" size="100%">Baselga, E</style></author><author><style face="normal" font="default" size="100%">Larcher, F</style></author><author><style face="normal" font="default" size="100%">Dopazo, J</style></author><author><style face="normal" font="default" size="100%">Del Rio, M</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Fibroblast activation and abnormal extracellular matrix remodelling as common hallmarks in three cancer-prone genodermatoses.</style></title><secondary-title><style face="normal" font="default" size="100%">Br J Dermatol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Br J Dermatol</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Biopsy</style></keyword><keyword><style  face="normal" font="default" size="100%">Blister</style></keyword><keyword><style  face="normal" font="default" size="100%">Case-Control Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Cells, Cultured</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Child, Preschool</style></keyword><keyword><style  face="normal" font="default" size="100%">Epidermolysis Bullosa</style></keyword><keyword><style  face="normal" font="default" size="100%">Epidermolysis Bullosa Dystrophica</style></keyword><keyword><style  face="normal" font="default" size="100%">Extracellular Matrix</style></keyword><keyword><style  face="normal" font="default" size="100%">Extracellular Matrix Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Fibroblasts</style></keyword><keyword><style  face="normal" font="default" size="100%">Fibrosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Healthy Volunteers</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant, Newborn</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Periodontal Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Photosensitivity Disorders</style></keyword><keyword><style  face="normal" font="default" size="100%">Primary Cell Culture</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA-seq</style></keyword><keyword><style  face="normal" font="default" size="100%">Skin</style></keyword><keyword><style  face="normal" font="default" size="100%">Xeroderma Pigmentosum</style></keyword><keyword><style  face="normal" font="default" size="100%">Young Adult</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019 09</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">181</style></volume><pages><style face="normal" font="default" size="100%">512-522</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer-prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders.&lt;/p&gt;&lt;p&gt;&lt;b&gt;OBJECTIVES: &lt;/b&gt;To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;We conducted RNA-Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA-Seq data. In addition, enzyme-linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury-sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS. What's already known about this topic? Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three genodermatoses with high predisposition to cancer development. Although their causal genetic mutations mainly affect epithelia, the dermal microenvironment likely contributes to the physiopathology of these disorders. What does this study add? We disclose a large overlapping transcription profile between XPC, KS and RDEB fibroblasts that points towards an activated phenotype with high matrix-synthetic capacity. This common signature seems to be independent of the primary causal deficiency, but reflects an underlying derangement of the extracellular matrix via transforming growth factor-β signalling activation and oxidative state imbalance. What is the translational message? This study broadens the current knowledge about the pathology of these diseases and highlights new targets and biomarkers for effective therapeutic intervention. It is suggested that high levels of circulating periostin could represent a potential biomarker in RDEB.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/30693469?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Pozo, María González-Del</style></author><author><style face="normal" font="default" size="100%">Bravo-Gil, Nereida</style></author><author><style face="normal" font="default" size="100%">Méndez-Vidal, Cristina</style></author><author><style face="normal" font="default" size="100%">Montero-de-Espinosa, Ignacio</style></author><author><style face="normal" font="default" size="100%">Millán, José M</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Borrego, Salud</style></author><author><style face="normal" font="default" size="100%">Antiňolo, Guillermo</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Re-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Med Genet A</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am J Med Genet A</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Base Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Cyclic Nucleotide Phosphodiesterases, Type 6</style></keyword><keyword><style  face="normal" font="default" size="100%">Extracellular Matrix Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Library</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation, Missense</style></keyword><keyword><style  face="normal" font="default" size="100%">Pedigree</style></keyword><keyword><style  face="normal" font="default" size="100%">Retinitis pigmentosa</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Analysis, DNA</style></keyword><keyword><style  face="normal" font="default" size="100%">Spain</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015 Jul</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">167</style></volume><pages><style face="normal" font="default" size="100%">1597-600</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Mutations in USH2A are a common cause of Retinitis Pigmentosa (RP). Among the most frequently reported USH2A variants, c.2276G&gt;T (p.C759F) has been found in both affected and healthy individuals. The pathogenicity of this variant remains controversial since it was detected in homozygosity in two healthy siblings of a Spanish family (S23), eleven years ago. The fact that these individuals remain asymptomatic today, prompted us to study the presence of other pathogenic variants in this family using targeted resequencing of 26 retinal genes in one of the affected individuals. This approach allowed us to identify one novel pathogenic homozygous mutation in exon 13 of PDE6B (c.1678C&gt;T; p.R560C). This variant cosegregated with the disease and was absent in 200 control individuals. Remarkably, the identified variant in PDE6B corresponds to the mutation responsible of the retinal degeneration in the naturally occurring rd10 mutant mice. To our knowledge, this is the first report of the identification of the rd10 mice mutation in a RP family. These findings, together with a review of the literature, support the hypothesis that homozygous p.C759F mutations are not pathogenic and led us to exclude the implication of p.C759F in the RP of family S23. Our results indicate the need of re-evaluating all families genetically diagnosed with this mutation.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">7</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/25823529?dopt=Abstract</style></custom1></record></records></xml>