<?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%">Colombo, Elisa A</style></author><author><style face="normal" font="default" size="100%">Locatelli, Andrea</style></author><author><style face="normal" font="default" size="100%">Cubells Sánchez, Laura</style></author><author><style face="normal" font="default" size="100%">Romeo, Sara</style></author><author><style face="normal" font="default" size="100%">Elcioglu, Nursel H</style></author><author><style face="normal" font="default" size="100%">Maystadt, Isabelle</style></author><author><style face="normal" font="default" size="100%">Esteve Martínez, Altea</style></author><author><style face="normal" font="default" size="100%">Sironi, Alessandra</style></author><author><style face="normal" font="default" size="100%">Fontana, Laura</style></author><author><style face="normal" font="default" size="100%">Finelli, Palma</style></author><author><style face="normal" font="default" size="100%">Gervasini, Cristina</style></author><author><style face="normal" font="default" size="100%">Pecile, Vanna</style></author><author><style face="normal" font="default" size="100%">Larizza, Lidia</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Rothmund-Thomson Syndrome: Insights from New Patients on the Genetic Variability Underpinning Clinical Presentation and Cancer Outcome.</style></title><secondary-title><style face="normal" font="default" size="100%">Int J Mol Sci</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Int J Mol Sci</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%">Cell Line, Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Homozygote</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Pedigree</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">RecQ Helicases</style></keyword><keyword><style  face="normal" font="default" size="100%">Rothmund-Thomson Syndrome</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 Apr 06</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">19</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Biallelic mutations in  gene, a caretaker of the genome, cause Rothmund-Thomson type-II syndrome (RTS-II) and confer increased cancer risk if they damage the helicase domain. We describe five families exemplifying clinical and allelic heterogeneity of RTS-II, and report the effect of pathogenic  variants by  predictions and transcripts analyses. Complete phenotype of patients #39 and #42 whose affected siblings developed osteosarcoma correlates with their c.[1048_1049del], c.[1878+32_1878+55del] and c.[1568G&gt;C;1573delT], c.[3021_3022del] variants which damage the helicase domain. Literature survey highlights enrichment of these variants affecting the helicase domain in patients with cancer outcome raising the issue of strict oncological surveillance. Conversely, patients #29 and #19 have a mild phenotype and carry, respectively, the unreported homozygous c.3265G&gt;T and c.3054A&gt;G variants, both sparing the helicase domain. Finally, despite matching several criteria for RTS clinical diagnosis, patient #38 is heterozygous for c.2412_2414del; no pathogenic CNVs out of those evidenced by high-resolution CGH-array, emerged as contributors to her phenotype.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">4</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/29642415?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%">Russo, Silvia</style></author><author><style face="normal" font="default" size="100%">Calzari, Luciano</style></author><author><style face="normal" font="default" size="100%">Mussa, Alessandro</style></author><author><style face="normal" font="default" size="100%">Mainini, Ester</style></author><author><style face="normal" font="default" size="100%">Cassina, Matteo</style></author><author><style face="normal" font="default" size="100%">Di Candia, Stefania</style></author><author><style face="normal" font="default" size="100%">Clementi, Maurizio</style></author><author><style face="normal" font="default" size="100%">Guzzetti, Sara</style></author><author><style face="normal" font="default" size="100%">Tabano, Silvia</style></author><author><style face="normal" font="default" size="100%">Miozzo, Monica</style></author><author><style face="normal" font="default" size="100%">Sirchia, Silvia</style></author><author><style face="normal" font="default" size="100%">Finelli, Palma</style></author><author><style face="normal" font="default" size="100%">Prontera, Paolo</style></author><author><style face="normal" font="default" size="100%">Maitz, Silvia</style></author><author><style face="normal" font="default" size="100%">Sorge, Giovanni</style></author><author><style face="normal" font="default" size="100%">Calcagno, Annalisa</style></author><author><style face="normal" font="default" size="100%">Maghnie, Mohamad</style></author><author><style face="normal" font="default" size="100%">Divizia, Maria Teresa</style></author><author><style face="normal" font="default" size="100%">Melis, Daniela</style></author><author><style face="normal" font="default" size="100%">Manfredini, Emanuela</style></author><author><style face="normal" font="default" size="100%">Ferrero, Giovanni Battista</style></author><author><style face="normal" font="default" size="100%">Pecile, Vanna</style></author><author><style face="normal" font="default" size="100%">Larizza, Lidia</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">A multi-method approach to the molecular diagnosis of overt and borderline 11p15.5 defects underlying Silver-Russell and Beckwith-Wiedemann syndromes.</style></title><secondary-title><style face="normal" font="default" size="100%">Clin Epigenetics</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Clin Epigenetics</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Beckwith-Wiedemann Syndrome</style></keyword><keyword><style  face="normal" font="default" size="100%">Blotting, Southern</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%">Chromosomes, Human, Pair 11</style></keyword><keyword><style  face="normal" font="default" size="100%">CpG Islands</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Methylation</style></keyword><keyword><style  face="normal" font="default" size="100%">Epigenesis, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</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%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mosaicism</style></keyword><keyword><style  face="normal" font="default" size="100%">Multiplex Polymerase Chain Reaction</style></keyword><keyword><style  face="normal" font="default" size="100%">Oligonucleotide Array Sequence Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Silver-Russell Syndrome</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">8</style></volume><pages><style face="normal" font="default" size="100%">23</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;Multiple (epi)genetic defects affecting the expression of the imprinted genes within the 11p15.5 chromosomal region underlie Silver-Russell (SRS) and Beckwith-Wiedemann (BWS) syndromes. The molecular diagnosis of these opposite growth disorders requires a multi-approach flowchart to disclose known primary and secondary (epi)genetic alterations; however, up to 20 and 30 % of clinically diagnosed BWS and SRS cases remain without molecular diagnosis. The complex structure of the 11p15 region with variable CpG methylation and low-rate mosaicism may account for missed diagnoses. Here, we demonstrate the relevance of complementary techniques for the assessment of different CpGs and the importance of testing multiple tissues to increase the SRS and BWS detection rate.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Molecular testing of 147 and 450 clinically diagnosed SRS and BWS cases provided diagnosis in 34 SRS and 185 BWS patients, with 9 SRS and 21 BWS cases remaining undiagnosed and herein referred to as &quot;borderline.&quot; A flowchart including complementary techniques and, when applicable, the analysis of buccal swabs, allowed confirmation of the molecular diagnosis in all borderline cases. Comparison of methylation levels by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in borderline and control cases defined an interval of H19/IGF2:IG-DMR loss of methylation that was distinct between &quot;easy to diagnose&quot; and &quot;borderline&quot; cases, which were characterized by values ≤mean -3 standard deviations (SDs) compared to controls. Values ≥mean +1 SD at H19/IGF2: IG-DMR were assigned to borderline hypermethylated BWS cases and those ≤mean -2 SD at KCNQ1OT1: TSS-DMR to hypomethylated BWS cases; these were supported by quantitative pyrosequencing or Southern blot analysis. Six BWS cases suspected to carry mosaic paternal uniparental disomy of chromosome 11 were confirmed by SNP array, which detected mosaicism till 10 %. Regarding the clinical presentation, borderline SRS were representative of the syndromic phenotype, with exception of one patient, whereas BWS cases showed low frequency of the most common features except hemihyperplasia.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;A conclusive molecular diagnosis was reached in borderline methylation cases, increasing the detection rate by 6 % for SRS and 5 % for BWS cases. The introduction of complementary techniques and additional tissue analyses into routine diagnostic work-up should facilitate the identification of cases undiagnosed because of mosaicism, a distinctive feature of epigenetic disorders.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/26933465?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%">Rusconi, Daniela</style></author><author><style face="normal" font="default" size="100%">Negri, Gloria</style></author><author><style face="normal" font="default" size="100%">Colapietro, Patrizia</style></author><author><style face="normal" font="default" size="100%">Picinelli, Chiara</style></author><author><style face="normal" font="default" size="100%">Milani, Donatella</style></author><author><style face="normal" font="default" size="100%">Spena, Silvia</style></author><author><style face="normal" font="default" size="100%">Magnani, Cinzia</style></author><author><style face="normal" font="default" size="100%">Silengo, Margherita Cirillo</style></author><author><style face="normal" font="default" size="100%">Sorasio, Lorena</style></author><author><style face="normal" font="default" size="100%">Curtisova, Vaclava</style></author><author><style face="normal" font="default" size="100%">Cavaliere, Maria Luigia</style></author><author><style face="normal" font="default" size="100%">Prontera, Paolo</style></author><author><style face="normal" font="default" size="100%">Stangoni, Gabriela</style></author><author><style face="normal" font="default" size="100%">Ferrero, Giovanni Battista</style></author><author><style face="normal" font="default" size="100%">Biamino, Elisa</style></author><author><style face="normal" font="default" size="100%">Fischetto, Rita</style></author><author><style face="normal" font="default" size="100%">Piccione, Maria</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Salviati, Leonardo</style></author><author><style face="normal" font="default" size="100%">Selicorni, Angelo</style></author><author><style face="normal" font="default" size="100%">Finelli, Palma</style></author><author><style face="normal" font="default" size="100%">Larizza, Lidia</style></author><author><style face="normal" font="default" size="100%">Gervasini, Cristina</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Characterization of 14 novel deletions underlying Rubinstein-Taybi syndrome: an update of the CREBBP deletion repertoire.</style></title><secondary-title><style face="normal" font="default" size="100%">Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Hum. Genet.</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%">Base Sequence</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%">Cohort Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">CREB-Binding Protein</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</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%">Point Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Rubinstein-Taybi Syndrome</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Deletion</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 Jun</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">134</style></volume><pages><style face="normal" font="default" size="100%">613-26</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Rubinstein-Taybi syndrome (RSTS) is a rare, clinically heterogeneous disorder characterized by cognitive impairment and several multiple congenital anomalies. The syndrome is caused by almost private point mutations in the CREBBP (~55% of cases) and EP300 (~8%) genes. The CREBBP mutational spectrum is variegated and characterized by point mutations (30-50 %) and deletions (~10%). The latter are diverse in size and genomic position and remove either the whole CREBBP gene and its flanking regions or only an intragenic portion. Here, we report 14 novel CREBBP deletions ranging from single exons to the whole gene and flanking regions which were identified by applying complementary cytomolecular techniques: fluorescence in situ hybridization, multiplex ligation-dependent probe amplification and array comparative genome hybridization, to a large cohort of RSTS patients. Deletions involving CREBBP account for 23% of our detected CREBBP mutations, making an important contribution to the mutational spectrum. Genotype-phenotype correlations revealed that patients with CREBBP deletions extending beyond this gene did not always have a more severe phenotype than patients harboring CREBBP point mutations, suggesting that neighboring genes play only a limited role in the etiopathogenesis of CREBBP-centerd contiguous gene syndrome. Accordingly, the extent of the deletion is not predictive of the severity of the clinical phenotype.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/25805166?dopt=Abstract</style></custom1></record></records></xml>