[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-432949-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-432949-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","stag2-truncating-variants-reveal-a-mosaic-stag2-inactivation-pattern-and-compensatory-mechanisms-involving-cohesin-complex-remodeling","STAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling","","STAG2-negative cells created by germline STAG2 truncating variants show an overall mosaic pattern of X chromosome inactivation that favors the mutant allele, leading to reduced or lost STAG2 expression. Despite the absence of obvious defects in sister chromatid cohesion or DNA repair, STAG2-deficient cells gain a proliferative advantage and display transcriptional remodeling. Compensatory mechanisms include upregulation of STAG1 and ectopic STAG3 incorporation, forming a previously unrecognized chimeric cohesin complex in somatic cells. These findings link molecular variability to phenotypic differences in STAG2-associated cohesinopathies.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/stag2-truncating-variants-reveal-a-mosaic-stag2-inactivation-pattern-and-compensatory-mechanisms-involving-cohesin-complex-remodeling/432949/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/stag2-truncating-variants-reveal-a-mosaic-stag2-inactivation-pattern-and-compensatory-mechanisms-involving-cohesin-complex-remodeling/432949.png","ImageObject",300,407,{"name":42,"@type":43},"Blue Pony","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-30","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":26},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What cellular pattern do STAG2-truncating variants produce in female fibroblasts?","Question",{"text":62,"@type":63},"They create highly skewed X chromosome inactivation that favors the mutant allele, causing loss of STAG2 expression in most cases and producing mosaic STAG2 expression.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"Do STAG2-deficient cells show defects in sister chromatid cohesion or DNA repair?",{"text":67,"@type":63},"No detectable defects were observed in sister chromatid cohesion or DNA repair, despite transcriptional changes.",{"name":69,"@type":60,"acceptedAnswer":70},"What compensatory mechanisms help counter STAG2 loss?",{"text":71,"@type":63},"The study reports compensatory upregulation of STAG1 and ectopic expression of the germ cell-specific paralog STAG3, which together enable formation of a chimeric cohesin complex in somatic cells.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},432949,1790791651,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":26,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},962090760266,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","iScience Article  \nSTAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling  \nAuthors  \nMacarena Moronta Gines,  \nMarja W. Wessels, Valentina Casa, ..., Jeroen Demmers, Wilfred F.J. van Ijcken, Kerstin S. Wendt  \nCorrespondence  \n[m.w.wessels@erasmusmc.nl](m.w.wessels@erasmusmc.nl) (M.W.W.),  \n[k.wendt@erasmusmc.nl](k.wendt@erasmusmc.nl) (K.S.W.)  \nIn brief  \nHealth sciences; Medicine; Clinical genetics; Biological sciences; Biochemistry; Physiology  \n• STAG2-negative cells seem to have a proliferative advantage over STAG2-positive cells  \n• STAG3 is expressed in 2 of 4 skin fibroblast samples and might substitute for STAG2  \nMoronta Gines et al., 2025, iScience 28, 114195  \nDecember 19, 2025 © 2025 The Authors. Published by Elsevier Inc.  \n[https://doi.org/10.1016/j.isci.2025.114195](https://doi.org/10.1016/j.isci.2025.114195)  \nll  \niScience  \nll  \nOPEN ACCESS  \nArticle  \nSTAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling  \nMacarena Moronta Gines,1,16 Marja W. Wessels,3,16,* Valentina Casa,1 Thomas van Staveren,1 Amber Hof,2  \nWendy K. Chung,4 Marjolaine Willems,5 Anna Sandestig,6,15 Irina Huening,7,8 Peter Turnpenny,9 Mathilde Lefebvre,10 Ilaria Parenti,11 Frank J. Kaiser,11 Jeroen Demmers,12,13 Wilfred F.J. van Ijcken,14 and Kerstin S. Wendt1,2,17,*  \n1Department of Cell Biology, Erasmus MC, 3015 GD Rotterdam, the Netherlands  \n2Department of Developmental Biology, Erasmus MC, 3015 GD Rotterdam, the Netherlands  \n3Department of Clinical Genetics, Erasmus MC, 3015 GD Rotterdam, the Netherlands  \n4Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA  \n5G´en´etique M´edicale, Reference Center for Constitutional Bone Diseases, CHU de MONTPELLIER, Institute for Neurosciences of Montpellier, University Montpellier, INSERM, 34295 Montpellier Cedex 05, France  \n6Clinical Department of Clinical Genetics, Region ¨Osterg¨otland, 581 85 Link¨oping, Sweden  \n7Institute of Human Genetics, University of Lu¨beck, 23562 Lu¨beck, Germany  \n8MVZ fu¨r Humangenetik und Molekularpathologie, 18059 Rostock, Germany  \n9Clinical Genetics, Royal Devon University Healthcare NHS Foundation Trust, Exeter EX1 2ED, UK  \n10UF de Foetopathologie, CHU d’Orleans, 45067 Orleans Cedex 2, France  \n11Institut fu¨r Humangenetik, Universit¨atsklinikum Essen, Universit¨at Duisburg-Essen, 45147 Essen, Germany  \n12Department of Biochemistry, Erasmus University Medical Center, 3015 GD Rotterdam, the Netherlands  \n13Proteomics Center, Erasmus University Medical Center, 3015 GD Rotterdam, the Netherlands  \n14Center for Biomics, Erasmus University Medical Center, 3015 GD, Rotterdam, the Netherlands  \n15Department of Biomedical and Clinical Sciences, Link¨oping University, Link¨oping, Sweden  \n16These authors contributed equally  \n17Lead contact  \n*[Correspondence:](Correspondence: m.w.wessels@erasmusmc.nl)[ m.w.wessels@erasmusmc.nl](Correspondence: m.w.wessels@erasmusmc.nl) (M.W.W.), [k.wendt@erasmusmc.nl](k.wendt@erasmusmc.nl) (K.S.W.) [https://doi.org/10.1016/j.isci.2025.114195](https://doi.org/10.1016/j.isci.2025.114195)  \nSUMMARY  \nCohesin plays a central role in three-dimensional genome organization and transcriptional regulation, with functional diversity determined by incorporation of distinct STAG subunits. Pathogenic variants in the X-linked STAG2 gene cause a rarecohesinopathy with variable clinical manifestations. Molecular analyses offibroblasts from females carrying germline STAG2-truncating variants revealed highly skewed X chromosome inactivation favoring the mutant allele, resulting in loss of STAG2 expression in most cases. STAG2-deficient cells displayed a proliferative advantage and transcriptional alterations without detectable defects in sister chromatid cohesion or DNA repair. Notably, compensatory upregulation of STAG1 and e","cbCaikAHvZ23ClbT","https://ap.wps.com/l/cbCaikAHvZ23ClbT","pdf",6925153,22,"English","# Summary\n# Introduction","[{\"question\":\"What cellular pattern do STAG2-truncating variants produce in female fibroblasts?\",\"answer\":\"They create highly skewed X chromosome inactivation that favors the mutant allele, causing loss of STAG2 expression in most cases and producing mosaic STAG2 expression.\"},{\"question\":\"Do STAG2-deficient cells show defects in sister chromatid cohesion or DNA repair?\",\"answer\":\"No detectable defects were observed in sister chromatid cohesion or DNA repair, despite transcriptional changes.\"},{\"question\":\"What compensatory mechanisms help counter STAG2 loss?\",\"answer\":\"The study reports compensatory upregulation of STAG1 and ectopic expression of the germ cell-specific paralog STAG3, which together enable formation of a chimeric cohesin complex in somatic cells.\"}]","STAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling | PDF",1790662053,55]