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The <jats:italic>ARID1B<\/jats:italic> protein, a subunit of the chromatin remodeling complex SWI\/SNF\u2010A, is involved in the regulation of transcription and multiple downstream cellular processes. We report here the clinical, genetic, and proteomic phenotypes of an individual with a unique apparent de novo mutation of <jats:italic>ARID1B<\/jats:italic> due to an intragenic duplication. His neurodevelopmental phenotype includes a severe speech\/language disorder with full scale IQ scores 78\u201398 and scattered academic skill levels, expanding the phenotypic spectrum of <jats:italic>ARID1B<\/jats:italic> mutations. Haploinsufficiency of <jats:italic>ARID1B<\/jats:italic> was determined both by RNA sequencing and quantitative RT\u2010PCR. Fluorescence in situ hybridization analysis supported an intragenic localization of the <jats:italic>ARID1B<\/jats:italic> copy number gain. Principal component analysis revealed marked differentiation of the subject's lymphoblast proteome from that of controls. Of 3426 proteins quantified, 1014 were significantly up\u2010 or down\u2010regulated compared to controls (<jats:italic>q<\/jats:italic>\u2009&lt;\u20090.01). Pathway analysis revealed highly significant enrichment for canonical pathways of EIF2 and EIF4 signaling, protein ubiquitination, tRNA charging and chromosomal replication, among others. Network analyses revealed down\u2010regulation of: (1) intracellular components involved in organization of membranes, organelles, and vesicles; (2) aspects of cell cycle control, signal transduction, and nuclear protein export; (3) ubiquitination and proteosomal function; and (4) aspects of mRNA synthesis\/splicing. Further studies are needed to determine the detailed molecular and cellular mechanisms by which constitutional haploinsufficiency of <jats:italic>ARID1B<\/jats:italic> causes syndromic and non\u2010syndromic developmental disabilities.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38327","type":"journal-article","created":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T11:26:53Z","timestamp":1499686013000},"page":"2478-2484","source":"Crossref","is-referenced-by-count":7,"title":["A novel microduplication of <i>ARID1B<\/i>: Clinical, genetic, and proteomic findings"],"prefix":"10.1002","volume":"173","author":[{"given":"Catarina M.","family":"Seabra","sequence":"first","affiliation":[{"name":"GABBA \u2212 Institute of Biomedical Sciences Abel Salazar of the University of Porto Porto Portugal"},{"name":"Molecular Neurogenetics Unit, Center for Genomic Medicine Massachusetts General Hospital Boston Massachusetts"},{"name":"Program in Medical and Population Genetics Broad Institute of MIT and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Szoko","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serkan","family":"Erdin","sequence":"additional","affiliation":[{"name":"Molecular Neurogenetics Unit, Center for Genomic Medicine Massachusetts General Hospital Boston Massachusetts"},{"name":"Program in Medical and Population Genetics Broad Institute of MIT and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashok","family":"Ragavendran","sequence":"additional","affiliation":[{"name":"Molecular Neurogenetics Unit, Center for Genomic Medicine Massachusetts General Hospital Boston Massachusetts"},{"name":"Program in Medical and Population Genetics Broad Institute of MIT and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexei","family":"Stortchevoi","sequence":"additional","affiliation":[{"name":"Molecular Neurogenetics Unit, Center for Genomic Medicine Massachusetts General Hospital Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcia","family":"Maciel","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Medicine University of Minho Braga Portugal"},{"name":"ICVS\/3Bs \u2212 PT Government Associate Laboratory Braga\/Guimar\u00e3es Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Lundberg","sequence":"additional","affiliation":[{"name":"Center for Proteomics Case Western Reserve University School of Medicine Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Schlatzer","sequence":"additional","affiliation":[{"name":"Center for Proteomics Case Western Reserve University School of Medicine Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Smith","sequence":"additional","affiliation":[{"name":"Baylor Genetics Laboratories Baylor College of Medicine Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E.","family":"Talkowski","sequence":"additional","affiliation":[{"name":"Molecular Neurogenetics Unit, Center for Genomic Medicine Massachusetts General Hospital Boston Massachusetts"},{"name":"Program in Medical and Population Genetics Broad Institute of MIT and Harvard Medical School Boston Massachusetts"},{"name":"Department of Neurology, Harvard Medical School Harvard University Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James F.","family":"Gusella","sequence":"additional","affiliation":[{"name":"Molecular Neurogenetics Unit, Center for Genomic Medicine Massachusetts General Hospital Boston Massachusetts"},{"name":"Program in Medical and Population Genetics Broad Institute of MIT and Harvard Medical School Boston Massachusetts"},{"name":"Department of Genetics, Harvard Medical School Harvard University Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3018-546X","authenticated-orcid":false,"given":"Marvin R.","family":"Natowicz","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine Cleveland Ohio"},{"name":"Pathology &amp; 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