{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:03:37Z","timestamp":1785233017852,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GSP15001"],"award-info":[{"award-number":["GSP15001"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K23NS119666"],"award-info":[{"award-number":["K23NS119666"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF20SA0064340"],"award-info":[{"award-number":["NNF20SA0064340"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>POU3F3<\/jats:italic>\n                    variants cause developmental delay, behavioral problems, hypotonia and dysmorphic features. We investigated the phenotypic and genetic landscape, and genotype\u2013phenotype correlations in individuals with POU3F3\u2010related disorders. We recruited unpublished individuals with\n                    <jats:italic>POU3F3<\/jats:italic>\n                    variants through international collaborations and obtained updated clinical data on previously published individuals. Trio exome sequencing or single exome sequencing followed by segregation analysis were performed in the novel cohort. Functional effects of missense variants were investigated with 3D protein modeling. We included 28 individuals (5 previously published) from 26 families carrying\n                    <jats:italic>POU3F3<\/jats:italic>\n                    variants; 23 de novo and one inherited from an affected parent. Median age at study inclusion was 7.4\u2009years. All had developmental delay mainly affecting speech, behavioral difficulties, psychiatric comorbidities and dysmorphisms. Additional features included gastrointestinal comorbidities, hearing loss, ophthalmological anomalies, epilepsy, sleep disturbances and joint hypermobility. Autism, hearing and eye comorbidities, dysmorphisms were more common in individuals with truncating variants, whereas epilepsy was only associated with missense variants. In silico structural modeling predicted that all (likely) pathogenic variants destabilize the DNA\u2010binding region of POU3F3. Our study refined the phenotypic and genetic landscape of POU3F3\u2010related disorders, it reports the functional properties of the identified pathogenic variants, and delineates some genotype\u2013phenotype correlations.\n                  <\/jats:p>","DOI":"10.1111\/cge.14353","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T02:50:14Z","timestamp":1683773414000},"page":"186-197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>POU3F3<\/scp>\n                    \u2010related disorder: Defining the phenotype and expanding the molecular spectrum"],"prefix":"10.1111","volume":"104","author":[{"given":"Alessandra","family":"Rossi","sequence":"first","affiliation":[{"name":"Department of Epilepsy Genetics and Personalized Medicine Danish Epilepsy Center, member of the ERN\u2010EpiCARE  Dianalund Denmark"},{"name":"Pediatric Clinic, IRCCS San Matteo Hospital Foundation University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lot Snijders","family":"Blok","sequence":"additional","affiliation":[{"name":"Human Genetics Department Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Neuser","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Kl\u00f6ckner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6127-6308","authenticated-orcid":false,"given":"Konrad","family":"Platzer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence Olivier","family":"Faivre","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, FHU TRANSLAD Centre Hospitalier Universitaire Dijon  Dijon France"},{"name":"Genetics of Developmental Disorders Team INSERM \u2013 Bourgogne Franche\u2010Comt\u00e9 University, UMR 1231 GAD  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Weigand","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Dr. von Hauner's Children's Hospital University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9505-5906","authenticated-orcid":false,"given":"Maria L.","family":"Dentici","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9, IRCCS  Rome Italy"},{"name":"Medical Genetics Unit, Academic Department of Pediatrics Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-9672","authenticated-orcid":false,"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4766-7753","authenticated-orcid":false,"given":"Marcello","family":"Niceta","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2197-9417","authenticated-orcid":false,"given":"Paolo","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Coulter","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lacey","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Vinorum","sequence":"additional","affiliation":[{"name":"Rikshospitalet Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerarda","family":"Cappuccio","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Federico II University  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine  Naples Italy"},{"name":"Scuola Superiore Meridionale School for Advanced Studies  Naples 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Aggregation Database (gnomAD v.2.1.1) POU3F3. Accessed 3 January 2023.https:\/\/gnomad.broadinstitute.org\/gene\/ENSG00000198914?dataset=gnomad_r2_1"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/2022.06.08.22276120"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1403"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.050106.093909"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14353","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T10:19:05Z","timestamp":1704190745000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1111\/cge.14353"],"URL":"https:\/\/doi.org\/10.1111\/cge.14353","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14353\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14353\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14353\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14353\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14353\/v1\/review2","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,10]]},"assertion":[{"value":"2023-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}