{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T13:40:03Z","timestamp":1778506803808,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T00:00:00Z","timestamp":1376611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["01GM08107"],"award-info":[{"award-number":["01GM08107"]}]},{"name":"BONFOR Program of the University of Bonn","award":["O-149.0096"],"award-info":[{"award-number":["O-149.0096"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Anorectal malformations (ARMs) comprise a broad spectrum of conditions ranging from mild anal anomalies to complex cloacal malformations. In 40\u201350% of cases, ARM occurs within the context of defined genetic syndromes or complex multiple congenital anomalies, such as VATER\/VACTERL (vertebral defects [V], ARMs [A], cardiac defects [C], tracheoesophageal fistula with or without esophageal atresia [TE], renal malformations [R], and limb defects [L]) association. Here, we report the identification of deletions at chromosome 13q using single nucleotide polymorphism\u2010based array analysis in two patients with mild ARM as part of VATER\/VACTERL and VATER\/VACTERL\u2010like associations. Both deletions overlap the previously defined critical region for ARM. Heterozygous <jats:italic>Efnb2<\/jats:italic> murine knockout models presenting with mild ARM suggest <jats:italic>EFNB2<\/jats:italic> as an excellent candidate gene in this region. Our patients showed a mild ARM phenotype, closely resembling that of the mouse. We performed a comprehensive mutation analysis of the <jats:italic>EFNB2<\/jats:italic> gene in 331 patients with isolated ARM, or ARM as part of VATER\/VACTERL or VATER\/VACTERL\u2010like associations. However, we did not identify any disease\u2010causing mutations. Given the convincing argument for <jats:italic>EFNB2<\/jats:italic> as a candidate gene for ARM, analyses of larger samples and screening of functionally relevant non\u2010coding regions of <jats:italic>EFNB2<\/jats:italic> are warranted. In conclusion, our report underlines the association of chromosome 13q deletions with ARM, suggesting that routine molecular diagnostic workup should include the search for these deletions. Despite the negative results of our mutation screening, we still consider <jats:italic>EFNB2<\/jats:italic> an excellent candidate gene for contributing to the development of ARM in humans. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36153","type":"journal-article","created":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T17:31:09Z","timestamp":1376674269000},"page":"3035-3041","source":"Crossref","is-referenced-by-count":35,"title":["De novo 13q deletions in two patients with mild anorectal malformations as part of VATER\/VACTERL and VATER\/VACTERL\u2010like association and analysis of <i>EFNB2<\/i> in patients with anorectal malformations"],"prefix":"10.1002","volume":"161","author":[{"given":"Gabriel C.","family":"Dworschak","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Draaken","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Genomics Life and Brain Center University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Marcelis","sequence":"additional","affiliation":[{"name":"Department of Genetics Radboud University Nijmegen Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivo","family":"de Blaauw","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Radboud University Nijmegen Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolph","family":"Pfundt","sequence":"additional","affiliation":[{"name":"Department of Genetics Radboud University Nijmegen Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris A.L.M.","family":"van Rooij","sequence":"additional","affiliation":[{"name":"Department for Health Evidence Radboud University Nijmegen Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrika","family":"Bartels","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Hilger","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekkehart","family":"Jenetzky","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research German Cancer Research Center Heidelberg Germany"},{"name":"Department of Child and Adolescent Psychiatry and Psychotherapy Johannes\u2010Gutenberg University Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eberhard","family":"Schmiedeke","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Pediatric Surgery and Urology Center for Child and Adolescent Health, Hospital Bremen\u2010Mitte Bremen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Grasshoff\u2010Derr","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery University Hospital W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Pediatric Surgery Campus Virchow Clinic Charite University Hospital Berlin Berlin 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Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Palta","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Evangelisches Krankenhaus Hamm Hamm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Leonhardt","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery St. Bernward\u2010Hospital Hildesheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattias","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Urology Cnopf'sche Kinderklinik N\u00fcrnberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Kujath","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery University of Greifswald Greifswald 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