{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:49:28Z","timestamp":1772992168558,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides\u2010Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in\n                    <jats:italic>SMARCA2<\/jats:italic>\n                    , that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM\u2010associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of\n                    <jats:italic>ADNP<\/jats:italic>\n                    present with the neurodevelopmental disorder known as Helsmoortel\u2010Van Der Aa Syndrome (HVDAS). Distinct DNA methylation profiles referred to as episignatures have been reported in HVDAS and BAF complex disorders. Due to molecular interactions between\n                    <jats:italic>ADNP<\/jats:italic>\n                    and BAF complex, and an overlapping craniofacial phenotype with narrowing of the palpebral fissures in a subset of patients with HVDAS and BIS, we hypothesized the possibility of a common phenotype\u2010specific episignature. A distinct episignature was shared by 15 individuals with BIS\u2010causing\n                    <jats:italic>SMARCA2<\/jats:italic>\n                    pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic\n                    <jats:italic>ADNP<\/jats:italic>\n                    variants. This represents first evidence of a sensitive phenotype\u2010specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene\u2010specific episignatures.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.c.32089","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T09:19:37Z","timestamp":1718615977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Blepharophimosis with intellectual disability and Helsmoortel\u2010Van Der Aa Syndrome share episignature and phenotype"],"prefix":"10.1002","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5274-8112","authenticated-orcid":false,"given":"Camilla","family":"Sarli","sequence":"first","affiliation":[{"name":"Department of Translational Medicine Federico II University of Naples  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7800-8665","authenticated-orcid":false,"given":"Liselot","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam Reproduction &amp; Development Research Institute, Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-9566","authenticated-orcid":false,"given":"Jack","family":"Reilly","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Western University  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0178-5327","authenticated-orcid":false,"given":"Slavica","family":"Trajkova","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Torino  Turin Italy"},{"name":"Molecular Biotechnology Center \u201cGuido Tarone\u201d University of Turin  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5690-6504","authenticated-orcid":false,"given":"Diana","family":"Carli","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Torino  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8318-7231","authenticated-orcid":false,"given":"Alfredo","family":"Brusco","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Torino  Turin Italy"},{"name":"Medical Genetics Unit Citt\u00e0 della Salute e della Scienza University Hospital  Turin Italy"},{"name":"Department of Neurosciences Rita Levi\u2010Montalcini University of Turin  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Levy","sequence":"additional","affiliation":[{"name":"Verspeeten Clinical Genome Centre London Health Science Centre  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8153-2222","authenticated-orcid":false,"given":"Raissa","family":"Relator","sequence":"additional","affiliation":[{"name":"Verspeeten Clinical Genome Centre London Health Science Centre  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1245-6606","authenticated-orcid":false,"given":"Jennifer","family":"Kerkhof","sequence":"additional","affiliation":[{"name":"Verspeeten Clinical Genome Centre London Health Science Centre  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haley","family":"McConkey","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Western University  London Ontario Canada"},{"name":"Verspeeten Clinical Genome Centre London Health Science Centre  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0613-6702","authenticated-orcid":false,"given":"Matthew L.","family":"Tedder","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7841-8277","authenticated-orcid":false,"given":"Cindy","family":"Skinner","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7386-4868","authenticated-orcid":false,"given":"Mari\u00eblle","family":"Alders","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam Reproduction &amp; Development Research Institute, Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2179-7808","authenticated-orcid":false,"given":"Peter","family":"Henneman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam Reproduction &amp; Development Research Institute, Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raoul C. M.","family":"Hennekam","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam Reproduction &amp; Development Research Institute, Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4100-7028","authenticated-orcid":false,"given":"Claudia","family":"Ciaccio","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-9418","authenticated-orcid":false,"given":"Stefano","family":"D'Arrigo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3717-8374","authenticated-orcid":false,"given":"Antonio","family":"Vitobello","sequence":"additional","affiliation":[{"name":"Department of Genetics, UNICAEN, Caen University Hospital Normandy University  Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9770-444X","authenticated-orcid":false,"given":"Laurence","family":"Faivre","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bourgogne, Inserm U1231, Equipe GAD  Dijon France"},{"name":"CHU Dijon Bourgogne, Centre de G\u00e9n\u00e9tique Centre de R\u00e9f\u00e9rence Maladies Rares \u201cAnomalies du D\u00e9veloppement et Syndromes Malformatifs\u201d, FHU\u2010TRANSLDAD  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9363-5141","authenticated-orcid":false,"given":"Sacha","family":"Weber","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique CHU de Caen\u2010Normandie  Caen France"},{"name":"Service de Neurologie CHU de Caen\u2010Normandie  Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline","family":"Vincent\u2010Devulder","sequence":"additional","affiliation":[{"name":"Department of Genetics, UNICAEN, Caen University Hospital Normandy University  Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Perrin","sequence":"additional","affiliation":[{"name":"Department of Genetics, UNICAEN, Caen University Hospital Normandy University  Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexia","family":"Bourgois","sequence":"additional","affiliation":[{"name":"Department of Genetics, UNICAEN, Caen University Hospital Normandy University  Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7540-5040","authenticated-orcid":false,"given":"Toshiyuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Gene Medicine, Graduate School of Medical Science Tokyo Women's Medical University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kay","family":"Metcalfe","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Health Innovation Manchester Manchester University Foundation NHS Trust  Manchester UK"},{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Zollino","sequence":"additional","affiliation":[{"name":"Institute of Genomic Medicine, Department of Life Sciences and Public Health 'Sacro Cuore' Catholic University of Rome  Rome Italy"},{"name":"Medical Genetics Unit Foundation IRCCS AOU Policlinico \u2018A. Gemelli\u2019  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Usha","family":"Kini","sequence":"additional","affiliation":[{"name":"Oxford Centre for Genomic Medicine Oxford University Hospitals NHS Foundation Trust  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Hospital Pedi\u00e1trico Centro Hospitalar e Universit\u00e1rio de Coimbra  Coimbra Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio B.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Hospital Pedi\u00e1trico Centro Hospitalar e Universit\u00e1rio de Coimbra  Coimbra Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Birmingham Women's &amp; Children's NHS Foundation Trust  Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3934-2342","authenticated-orcid":false,"given":"Gerarda","family":"Cappuccio","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Federico II University of Naples  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bekim","family":"Sadikovic","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam Reproduction &amp; Development Research Institute, Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Pathology and Laboratory Medicine Western University  London Ontario Canada"},{"name":"Verspeeten Clinical Genome Centre London Health Science Centre  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-8819","authenticated-orcid":false,"given":"Nicola","family":"Brunetti\u2010Pierri","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Federico II University of Naples  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"},{"name":"Scuola Superiore Meridionale (SSM, School of Advanced Studies), Genomics and Experimental Medicine Program University of Naples Federico II  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.03.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.01.019"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu049"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-019-0658-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.07.003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0898-y"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2018.1471313"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab819"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx183"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-023-01450-8"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11192994"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu393"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2899"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v042.i08"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37641"},{"issue":"1","key":"e_1_2_10_17_1","article-title":"Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders","volume":"3","author":"Levy M. 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