{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:21:32Z","timestamp":1787008892252,"version":"build-2736575974"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T00:00:00Z","timestamp":1605398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100016685","name":"Baylor-Hopkins Center for Mendelian Genomics","doi-asserted-by":"crossref","award":["UM1 HG006542"],"award-info":[{"award-number":["UM1 HG006542"]}],"id":[{"id":"10.13039\/100016685","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03HD099516"],"award-info":[{"award-number":["R03HD099516"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["R01DK080099"],"award-info":[{"award-number":["R01DK080099"]}]},{"name":"MSD Avenir"},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-IAHU-01"],"award-info":[{"award-number":["ANR-10-IAHU-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NSW Government"},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["ID1042002"],"award-info":[{"award-number":["ID1042002"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["ID1135886"],"award-info":[{"award-number":["ID1135886"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["ID1044543"],"award-info":[{"award-number":["ID1044543"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The genetic causes of multiple congenital anomalies are incompletely understood. Here, we report novel heterozygous predicted loss-of-function (LoF) and predicted damaging missense variants in the WW domain binding protein 11 (WBP11) gene in seven unrelated families with a variety of overlapping congenital malformations, including cardiac, vertebral, tracheo-esophageal, renal and limb defects. WBP11 encodes a component of the spliceosome with the ability to activate pre-messenger RNA splicing. We generated a Wbp11 null allele in mouse using CRISPR-Cas9 targeting. Wbp11 homozygous null embryos die prior to E8.5, indicating that Wbp11 is essential for development. Fewer Wbp11 heterozygous null mice are found than expected due to embryonic and postnatal death. Importantly, Wbp11 heterozygous null mice are small and exhibit defects in axial skeleton, kidneys and esophagus, similar to the affected individuals, supporting the role of WBP11 haploinsufficiency in the development of congenital malformations in humans. LoF WBP11 variants should be considered as a possible cause of VACTERL association as well as isolated Klippel-Feil syndrome, renal agenesis or esophageal atresia.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa258","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T09:25:07Z","timestamp":1606901107000},"page":"3662-3678","source":"Crossref","is-referenced-by-count":26,"title":["Heterozygous loss of\n                    <i>WBP11<\/i>\n                    function causes multiple congenital defects in humans and mice"],"prefix":"10.1093","volume":"29","author":[{"given":"Ella M M A","family":"Martin","sequence":"first","affiliation":[{"name":"Development & Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle","family":"Enriquez","sequence":"additional","affiliation":[{"name":"Development & Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney 2010, Australia"},{"name":"Faculty of Medicine, UNSW, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan B","family":"Sparrow","sequence":"additional","affiliation":[{"name":"Development & Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney 2010, Australia"},{"name":"Faculty of Science, UNSW, Sydney 2052, Australia"},{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T","family":"Humphreys","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, UNSW, Sydney 2052, Australia"},{"name":"Molecular, Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, Sydney 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aideen M","family":"McInerney-Leo","sequence":"additional","affiliation":[{"name":"Dermatology Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Leo","sequence":"additional","affiliation":[{"name":"Translational Genomics Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L","family":"Duncan","sequence":"additional","affiliation":[{"name":"Translational Genomics Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba 4102, Australia"},{"name":"Department of Twin Research & Genetic Epidemiology, Faculty of Life Sciences and Medicine, School of Life Course Sciences, King\u2019s College London, London SE1 7EH, UK"},{"name":"Faculty of Medicine, University of Queensland, Herston 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavitha R","family":"Iyer","sequence":"additional","affiliation":[{"name":"Development & Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelene A","family":"Greasby","sequence":"additional","affiliation":[{"name":"Development & Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4767-7583","authenticated-orcid":false,"given":"Eddie","family":"Ip","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, UNSW, Sydney 2052, Australia"},{"name":"Computational Genomics Laboratory, Victor Chang Cardiac Research Institute, Sydney 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Giannoulatou","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, UNSW, Sydney 2052, Australia"},{"name":"Computational Genomics Laboratory, Victor Chang Cardiac Research Institute, Sydney 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delicia","family":"Sheng","sequence":"additional","affiliation":[{"name":"Development & Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Wohler","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University, Baltimore 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mantine","family":"Dimartino","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics of Human Malformations, Institute National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) UMR 1163, Institut Imagine, Paris 75015, France"},{"name":"Paris Descartes-Sorbonne Paris Cit\u00e9 Universit\u00e9, Institut Imagine, Paris 75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Amiel","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics of Human Malformations, Institute National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) UMR 1163, Institut Imagine, Paris 75015, France"},{"name":"Paris Descartes-Sorbonne Paris Cit\u00e9 Universit\u00e9, Institut Imagine, Paris 75015, France"},{"name":"D\u00e9partement de G\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris, Paris 75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yline","family":"Capri","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique, H\u00f4pital Robert Debr\u00e9, Assistance Publique H\u00f4pitaux de Paris, Paris 75019, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphn\u00e9","family":"Lehalle","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Intercommunal Cr\u00e9teil, Cr\u00e9teil 94000, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Mory","sequence":"additional","affiliation":[{"name":"The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Wilnai","sequence":"additional","affiliation":[{"name":"The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Lebenthal","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, 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D","family":"Steiner","sequence":"additional","affiliation":[{"name":"Marshfield Clinic Health System, Marshfield, WI 54449, USA"},{"name":"University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Raggio","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery, Pediatrics Orthopedic Surgery, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Blank","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagit","family":"Baris Feldman","sequence":"additional","affiliation":[{"name":"The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, 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Malformations, Institute National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) UMR 1163, Institut Imagine, Paris 75015, France"},{"name":"Paris Descartes-Sorbonne Paris Cit\u00e9 Universit\u00e9, Institut Imagine, Paris 75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip F","family":"Giampietro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Illinois-Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2056-2820","authenticated-orcid":false,"given":"Sally L","family":"Dunwoodie","sequence":"additional","affiliation":[{"name":"Development & Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney 2010, Australia"},{"name":"Faculty of Medicine, UNSW, Sydney 2052, Australia"},{"name":"Faculty of Science, UNSW, Sydney 2052, 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