<?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%">Flex, Elisabetta</style></author><author><style face="normal" font="default" size="100%">Martinelli, Simone</style></author><author><style face="normal" font="default" size="100%">Van Dijck, Anke</style></author><author><style face="normal" font="default" size="100%">Ciolfi, Andrea</style></author><author><style face="normal" font="default" size="100%">Cecchetti, Serena</style></author><author><style face="normal" font="default" size="100%">Coluzzi, Elisa</style></author><author><style face="normal" font="default" size="100%">Pannone, Luca</style></author><author><style face="normal" font="default" size="100%">Andreoli, Cristina</style></author><author><style face="normal" font="default" size="100%">Radio, Francesca Clementina</style></author><author><style face="normal" font="default" size="100%">Pizzi, Simone</style></author><author><style face="normal" font="default" size="100%">Carpentieri, Giovanna</style></author><author><style face="normal" font="default" size="100%">Bruselles, Alessandro</style></author><author><style face="normal" font="default" size="100%">Catanzaro, Giuseppina</style></author><author><style face="normal" font="default" size="100%">Pedace, Lucia</style></author><author><style face="normal" font="default" size="100%">Miele, Evelina</style></author><author><style face="normal" font="default" size="100%">Carcarino, Elena</style></author><author><style face="normal" font="default" size="100%">Ge, Xiaoyan</style></author><author><style face="normal" font="default" size="100%">Chijiwa, Chieko</style></author><author><style face="normal" font="default" size="100%">Lewis, M E Suzanne</style></author><author><style face="normal" font="default" size="100%">Meuwissen, Marije</style></author><author><style face="normal" font="default" size="100%">Kenis, Sandra</style></author><author><style face="normal" font="default" size="100%">Van der Aa, Nathalie</style></author><author><style face="normal" font="default" size="100%">Larson, Austin</style></author><author><style face="normal" font="default" size="100%">Brown, Kathleen</style></author><author><style face="normal" font="default" size="100%">Wasserstein, Melissa P</style></author><author><style face="normal" font="default" size="100%">Skotko, Brian G</style></author><author><style face="normal" font="default" size="100%">Begtrup, Amber</style></author><author><style face="normal" font="default" size="100%">Person, Richard</style></author><author><style face="normal" font="default" size="100%">Karayiorgou, Maria</style></author><author><style face="normal" font="default" size="100%">Roos, J Louw</style></author><author><style face="normal" font="default" size="100%">Van Gassen, Koen L</style></author><author><style face="normal" font="default" size="100%">Koopmans, Marije</style></author><author><style face="normal" font="default" size="100%">Bijlsma, Emilia K</style></author><author><style face="normal" font="default" size="100%">Santen, Gijs W E</style></author><author><style face="normal" font="default" size="100%">Barge-Schaapveld, Daniela Q C M</style></author><author><style face="normal" font="default" size="100%">Ruivenkamp, Claudia A L</style></author><author><style face="normal" font="default" size="100%">Hoffer, Mariette J V</style></author><author><style face="normal" font="default" size="100%">Lalani, Seema R</style></author><author><style face="normal" font="default" size="100%">Streff, Haley</style></author><author><style face="normal" font="default" size="100%">Craigen, William J</style></author><author><style face="normal" font="default" size="100%">Graham, Brett H</style></author><author><style face="normal" font="default" size="100%">van den Elzen, Annette P M</style></author><author><style face="normal" font="default" size="100%">Kamphuis, Daan J</style></author><author><style face="normal" font="default" size="100%">Õunap, Katrin</style></author><author><style face="normal" font="default" size="100%">Reinson, Karit</style></author><author><style face="normal" font="default" size="100%">Pajusalu, Sander</style></author><author><style face="normal" font="default" size="100%">Wojcik, Monica H</style></author><author><style face="normal" font="default" size="100%">Viberti, Clara</style></author><author><style face="normal" font="default" size="100%">Di Gaetano, Cornelia</style></author><author><style face="normal" font="default" size="100%">Bertini, Enrico</style></author><author><style face="normal" font="default" size="100%">Petrucci, Simona</style></author><author><style face="normal" font="default" size="100%">De Luca, Alessandro</style></author><author><style face="normal" font="default" size="100%">Rota, Rossella</style></author><author><style face="normal" font="default" size="100%">Ferretti, Elisabetta</style></author><author><style face="normal" font="default" size="100%">Matullo, Giuseppe</style></author><author><style face="normal" font="default" size="100%">Dallapiccola, Bruno</style></author><author><style face="normal" font="default" size="100%">Sgura, Antonella</style></author><author><style face="normal" font="default" size="100%">Walkiewicz, Magdalena</style></author><author><style face="normal" font="default" size="100%">Kooy, R Frank</style></author><author><style face="normal" font="default" size="100%">Tartaglia, Marco</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Aberrant Function of the C-Terminal Tail of HIST1H1E Accelerates Cellular Senescence and Causes Premature Aging.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am. J. Hum. Genet.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019 Sep 05</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">105</style></volume><pages><style face="normal" font="default" size="100%">493-508</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Histones mediate dynamic packaging of nuclear DNA in chromatin, a process that is precisely controlled to guarantee efficient compaction of the genome and proper chromosomal segregation during cell division and to accomplish DNA replication, transcription, and repair. Due to the important structural and regulatory roles played by histones, it is not surprising that histone functional dysregulation or aberrant levels of histones can have severe consequences for multiple cellular processes and ultimately might affect development or contribute to cell transformation. Recently, germline frameshift mutations involving the C-terminal tail of HIST1H1E, which is a widely expressed member of the linker histone family and facilitates higher-order chromatin folding, have been causally linked to an as-yet poorly defined syndrome that includes intellectual disability. We report that these mutations result in stable proteins that reside in the nucleus, bind to chromatin, disrupt proper compaction of DNA, and are associated with a specific methylation pattern. Cells expressing these mutant proteins have a dramatically reduced proliferation rate and competence, hardly enter into the S phase, and undergo accelerated senescence. Remarkably, clinical assessment of a relatively large cohort of subjects sharing these mutations revealed a premature aging phenotype as a previously unrecognized feature of the disorder. Our findings identify a direct link between aberrant chromatin remodeling, cellular senescence, and accelerated aging.&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/31447100?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%">Posey, Jennifer E</style></author><author><style face="normal" font="default" size="100%">Harel, Tamar</style></author><author><style face="normal" font="default" size="100%">Liu, Pengfei</style></author><author><style face="normal" font="default" size="100%">Rosenfeld, Jill A</style></author><author><style face="normal" font="default" size="100%">James, Regis A</style></author><author><style face="normal" font="default" size="100%">Coban Akdemir, Zeynep H</style></author><author><style face="normal" font="default" size="100%">Walkiewicz, Magdalena</style></author><author><style face="normal" font="default" size="100%">Bi, Weimin</style></author><author><style face="normal" font="default" size="100%">Xiao, Rui</style></author><author><style face="normal" font="default" size="100%">Ding, Yan</style></author><author><style face="normal" font="default" size="100%">Xia, Fan</style></author><author><style face="normal" font="default" size="100%">Beaudet, Arthur L</style></author><author><style face="normal" font="default" size="100%">Muzny, Donna M</style></author><author><style face="normal" font="default" size="100%">Gibbs, Richard A</style></author><author><style face="normal" font="default" size="100%">Boerwinkle, Eric</style></author><author><style face="normal" font="default" size="100%">Eng, Christine M</style></author><author><style face="normal" font="default" size="100%">Sutton, V Reid</style></author><author><style face="normal" font="default" size="100%">Shaw, Chad A</style></author><author><style face="normal" font="default" size="100%">Plon, Sharon E</style></author><author><style face="normal" font="default" size="100%">Yang, Yaping</style></author><author><style face="normal" font="default" size="100%">Lupski, James R</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation.</style></title><secondary-title><style face="normal" font="default" size="100%">N Engl J Med</style></secondary-title><alt-title><style face="normal" font="default" size="100%">N Engl J Med</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Exome</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Diseases, Inborn</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Variation</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotyping Techniques</style></keyword><keyword><style  face="normal" font="default" size="100%">High-Throughput Nucleotide Sequencing</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Retrospective Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Analysis, DNA</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 Jan 05</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">376</style></volume><pages><style face="normal" font="default" size="100%">21-31</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;Whole-exome sequencing can provide insight into the relationship between observed clinical phenotypes and underlying genotypes.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;We conducted a retrospective analysis of data from a series of 7374 consecutive unrelated patients who had been referred to a clinical diagnostic laboratory for whole-exome sequencing; our goal was to determine the frequency and clinical characteristics of patients for whom more than one molecular diagnosis was reported. The phenotypic similarity between molecularly diagnosed pairs of diseases was calculated with the use of terms from the Human Phenotype Ontology.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;A molecular diagnosis was rendered for 2076 of 7374 patients (28.2%); among these patients, 101 (4.9%) had diagnoses that involved two or more disease loci. We also analyzed parental samples, when available, and found that de novo variants accounted for 67.8% (61 of 90) of pathogenic variants in autosomal dominant disease genes and 51.7% (15 of 29) of pathogenic variants in X-linked disease genes; both variants were de novo in 44.7% (17 of 38) of patients with two monoallelic variants. Causal copy-number variants were found in 12 patients (11.9%) with multiple diagnoses. Phenotypic similarity scores were significantly lower among patients in whom the phenotype resulted from two distinct mendelian disorders that affected different organ systems (50 patients) than among patients with disorders that had overlapping phenotypic features (30 patients) (median score, 0.21 vs. 0.36; P=1.77×10).&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;In our study, we found multiple molecular diagnoses in 4.9% of cases in which whole-exome sequencing was informative. Our results show that structured clinical ontologies can be used to determine the degree of overlap between two mendelian diseases in the same patient; the diseases can be distinct or overlapping. Distinct disease phenotypes affect different organ systems, whereas overlapping disease phenotypes are more likely to be caused by two genes encoding proteins that interact within the same pathway. (Funded by the National Institutes of Health and the Ting Tsung and Wei Fong Chao Foundation.).&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/27959697?dopt=Abstract</style></custom1></record></records></xml>