{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:50:02Z","timestamp":1785527402291,"version":"3.56.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The caudal type homeobox 2 (\n                    <jats:italic>CDX2<\/jats:italic>\n                    ) gene encodes a developmental regulator involved in caudal body patterning. Only three pathogenic variants in human\n                    <jats:italic>CDX2<\/jats:italic>\n                    have been described, in patients with persistent cloaca, sirenomelia and\/or renal and anogenital malformations. We identified five patients with de novo or inherited pathogenic variants in\n                    <jats:italic>CDX2<\/jats:italic>\n                    with clinical phenotypes that partially overlap with previous cases, that is, imperforate anus and renal, urogenital and limb abnormalities. However, additional clinical features were seen including vertebral agenesis and we describe considerable phenotypic variability, even in unrelated patients with the same recurrent p.(Arg237His) variant. We propose\n                    <jats:italic>CDX2<\/jats:italic>\n                    variants as rare genetic cause for a multiple congenital anomaly syndrome that can include features of caudal regression syndrome and VACTERL. A causative role is further substantiated by the relationship between CDX2 and other proteins encoded by genes that were previously linked to caudal abnormalities in humans, for example,\n                    <jats:italic>TBXT<\/jats:italic>\n                    (sacral agenesis and other vertebral segmentation defects) and\n                    <jats:italic>CDX1<\/jats:italic>\n                    (anorectal malformations). Our findings confirm the essential role of\n                    <jats:italic>CDX2<\/jats:italic>\n                    in caudal morphogenesis and formation of cloacal derivatives in humans, which to date has only been well characterized in animals.\n                  <\/jats:p>","DOI":"10.1111\/cge.14076","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T22:40:58Z","timestamp":1634769658000},"page":"183-189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The broader phenotypic spectrum of congenital caudal abnormalities associated with mutations in the caudal type homeobox 2 gene"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8769-3150","authenticated-orcid":false,"given":"Servi J. C.","family":"Stevens","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University Medical Centre and GROW School for Oncology and Developmental Biology Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constance T. R. M.","family":"Stumpel","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University Medical Centre and GROW School for Oncology and Developmental Biology Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin E. M.","family":"Diderich","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Centre  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjon A.","family":"van Slegtenhorst","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Centre  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary\u2010Alice","family":"Abbott","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Massachusetts Medical School\u2010Baystate  Springfield Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Manning","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Massachusetts Medical School\u2010Baystate  Springfield Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorune","family":"Balciuniene","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and the Roberts Individualized Medical Genetics Center Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise C.","family":"Pyle","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and the Roberts Individualized Medical Genetics Center Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Leonard","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and the Roberts Individualized Medical Genetics Center Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill R.","family":"Murrell","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and the Roberts Individualized Medical Genetics Center Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy","family":"van de Putte","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris A. 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M.","family":"van Rooij","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hoischen","sequence":"additional","affiliation":[{"name":"Department of Genetics Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Lasko","sequence":"additional","affiliation":[{"name":"Department of Genetics Radboud University Medical Centre  Nijmegen the Netherlands"},{"name":"Department of Biology McGill University  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han G.","family":"Brunner","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University Medical Centre and GROW School for Oncology and Developmental Biology 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