{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:58:19Z","timestamp":1789916299451,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bainbridge\u2013Ropers Syndrome (BRPS) is a genetic condition resulting from truncating variants in the\n                    <jats:italic>ASXL3<\/jats:italic>\n                    gene. The clinical features include neurodevelopmental and language impairments, behavioral issues, hypotonia, feeding difficulties, and distinctive facial features. In this retrospective study, we analyzed 22 Spanish individuals with BRPS, aiming to perform a detailed clinical and molecular description and establish a genotype\u2013phenotype correlation. We identified 19\n                    <jats:italic>ASXL3<\/jats:italic>\n                    variants, nine of which are novel. We documented recurrence in nontwin siblings due to parental mosaicism. The predominant prenatal finding was intrauterine growth restriction (35%) followed, after birth, by feeding difficulties (90.5%), hypotonia (85.7%), and gastroesophageal reflux disease (82.4%). Later in life, intellectual disability, language impairment, autism spectrum disorder (75%), and joint laxity (73.7%) were noted. Individuals with variants in the 3\u2032 mutational cluster region (MCR) of exon 12 exhibited more perinatal feeding problems, and those with variants in the 5\u2032 MCR of exon 11 displayed lower percentiles in height and occipitofrontal circumference, as well as higher frequency of arched eyebrows. This study is the first characterization of a Spanish BRPS cohort, with more than 50 clinical features analyzed, representing the most detailed phenotypic analysis to date.\n                  <\/jats:p>","DOI":"10.1111\/cge.14701","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T22:13:27Z","timestamp":1737411207000},"page":"646-662","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Comprehensive Clinical and Genetic Characterization of a Spanish Cohort of 22 Patients With Bainbridge\u2013Ropers Syndrome"],"prefix":"10.1111","volume":"107","author":[{"given":"Laura","family":"Trujillano","sequence":"first","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Costa\u2010Roger","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivon","family":"Cusc\u00f3","sequence":"additional","affiliation":[{"name":"Genetics Department, Institut d'Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU) Hospital de la Santa Creu i Sant Pau  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Fernandez\u2010Alvarez","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cueto\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaia","family":"Lasa\u2010Aranzasti","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara","family":"Masotto","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Abul\u00ed","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Codina\u2010Sol\u00e0","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"del Campo","sequence":"additional","affiliation":[{"name":"Department of Clinical Pediatrics University of California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"Ruiz Moreno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hospital Costa del Sol  Marbella M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Pardo Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hospital Costa del Sol  Marbella M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Palma Milla","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica Hospital Universitario 12 de Octubre  Madrid Spain"},{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica) Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2749-2709","authenticated-orcid":false,"given":"Rub\u00e9n","family":"P\u00e9rez de la Fuente","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica Hospital Universitario 12 de Octubre  Madrid Spain"},{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica) Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-5214","authenticated-orcid":false,"given":"Juan Francisco","family":"Quesada\u2010Espinosa","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica Hospital Universitario 12 de Octubre  Madrid Spain"},{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica) Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noem\u00ed","family":"N\u00fa\u00f1ez\u2010Enamorado","sequence":"additional","affiliation":[{"name":"Departamento de Neurolog\u00eda pedi\u00e1trica Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Gener","sequence":"additional","affiliation":[{"name":"Department of Genetics Cruces University Hospital, Biobizkaia Health Research Institute  Vizcaya Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Juliana","family":"Ballesta\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Secci\u00f3n Gen\u00e9tica M\u00e9dica, Servicio de Pediatr\u00eda Hospital Clinico Universitario Virgen de la Arrixaca  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1527-471X","authenticated-orcid":false,"given":"Alejandro J.","family":"Brea\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Grupo de Gen\u00f3mica y Bioinform\u00e1tica, Centro Singular de Investigaci\u00f3n en Medicina Molecular y Enfermedades Cr\u00f3nicas (CiMUS), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras del Instituto de Salud Carlos III (CIBERER\u2010ISCIII) Universidade de Santiago de Compostela  Santiago de Compostela Spain"},{"name":"Fundaci\u00f3n P\u00fablica Galega Instituto de Investigaci\u00f3n Sanitaria de Santiago de Compostela (FIDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montse","family":"Fern\u00e1ndez\u2010Prieto","sequence":"additional","affiliation":[{"name":"Grupo de Gen\u00f3mica y Bioinform\u00e1tica, Centro Singular de Investigaci\u00f3n en Medicina Molecular y Enfermedades Cr\u00f3nicas (CiMUS), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras del Instituto de Salud Carlos III (CIBERER\u2010ISCIII) Universidade de Santiago de Compostela  Santiago de Compostela Spain"},{"name":"Fundaci\u00f3n P\u00fablica Galega Instituto de Investigaci\u00f3n Sanitaria de Santiago de Compostela (FIDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Trujillo\u2010Quintero","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Parc Taul\u00ed Hospital Universitari, Institut d'Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT\u2010CERCA) Universitat Aut\u00f2noma de Barcelona  Sabadell Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7314-5962","authenticated-orcid":false,"given":"Anna","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Parc Taul\u00ed Hospital Universitari, Institut d'Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT\u2010CERCA) Universitat Aut\u00f2noma de Barcelona  Sabadell Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Santos\u2010Simarro","sequence":"additional","affiliation":[{"name":"Unidad de Diagn\u00f3stico Molecular y Gen\u00e9tica Cl\u00ednica Hospital Universitario Son Espases  Idisba Palma de Mallorca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Rosello","sequence":"additional","affiliation":[{"name":"Genetics Unit Hospital Universitario y Politecnico La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Orellana","sequence":"additional","affiliation":[{"name":"Genetics Unit Hospital Universitario y Politecnico La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Martinez","sequence":"additional","affiliation":[{"name":"Genetics Unit Hospital Universitario y Politecnico La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio F.","family":"Martinez\u2010Monseny","sequence":"additional","affiliation":[{"name":"Department of Genetics and Institut de Recerca Hospital Sant Joan de D\u00e9u Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00eddac","family":"Casas\u2010Alba","sequence":"additional","affiliation":[{"name":"Department of Genetics and Institut de Recerca Hospital Sant Joan de D\u00e9u Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Serrano","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Institut de Recerca Hospital Sant Joan de D\u00e9u  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2727-7654","authenticated-orcid":false,"given":"Mar\u00eda","family":"Palomares\u2010Bralo","sequence":"additional","affiliation":[{"name":"Clinical Genetics Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, CIBERER Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Rikeros\u2010Orozco","sequence":"additional","affiliation":[{"name":"Clinical Genetics Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, CIBERER Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda \u00c1ngeles","family":"G\u00f3mez\u2010Cano","sequence":"additional","affiliation":[{"name":"Clinical Genetics Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, CIBERER Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Tirado\u2010Requero","sequence":"additional","affiliation":[{"name":"Neuropediatric Unit University Hospital La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Pi\u00e9 Juste","sequence":"additional","affiliation":[{"name":"Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology\u2010Physiology, School of Medicine Universidad de Zaragoza, CIBERER\u2010GCV02 and IIS\u2010Aragon  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feliciano J.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology\u2010Physiology, School of Medicine Universidad de Zaragoza, CIBERER\u2010GCV02 and IIS\u2010Aragon  Zaragoza Spain"},{"name":"Unit of Clinical Genetics, Service of Paediatrics University Hospital \u2018Lozano Blesa\u2019, University of Zaragoza Medical School, CIBERER\u2010GCV02 and IIS\u2010Aragon  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Garc\u00eda\u2010Arum\u00ed","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo F.","family":"Tizzano","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Area Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm415"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00075"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm420"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755\u20108794\u20106\u201032"},{"issue":"6","key":"e_1_2_9_6_1","first-page":"1617","article-title":"Identification and Characterization of ASXL3 Gene In Silico","volume":"24","author":"Katoh M.","year":"2004","journal-title":"International Journal of Oncology"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1586\/14789450.2015.1033409"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv499"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.868"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37653"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.017"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14135"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62465"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14506"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102020\u2010107604"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2020.104107"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102016\u2010104360"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.165"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a002410"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2018.01.014"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2020.103925"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1191"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20191"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1352\/1944\u20107558\u2010115\u20105.364"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887\u2010020\u201002027\u20107"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.1361"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2019.10303"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0968\u20100004(98)01208\u20100"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14701","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T22:56:39Z","timestamp":1746399399000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,20]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/cge.14701"],"URL":"https:\/\/doi.org\/10.1111\/cge.14701","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14701\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14701\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14701\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14701\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14701\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,20]]},"assertion":[{"value":"2024-10-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}