{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:15:07Z","timestamp":1787004907202,"version":"build-2736575974"},"reference-count":21,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr Surg"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Introduction\u2003The VACTERL association is a rare malformation complex, showing at least three anomalies of the following organ systems: vertebra, anorectum, heart and vessels, trachea and esophagus, genitourinary tract, and limbs. In addition to a multifactorial event, congenital vascular disorders are also discussed as triggers for the VACTERL association. The aim of this study was to determine whether there is a genetic background for vascular disorders triggering VACTERL association.<\/jats:p>\n                  <jats:p>Materials and Methods\u2003We performed a functional analysis on whole exome sequencing data of 21 patients with VACTERL or VACTERL-like phenotype using the online analysis tool \u201cDatabase for Annotation, Visualization and Integrated Discovery (DAVID) v6.8.\u201d The study was approved by the institutional ethics committee (approval no. 026\u201313). Written informed consent was obtained from all patients or their parents.<\/jats:p>\n                  <jats:p>Results\u2003We identified a total of 86 genetic variants (in 75 genes) classified as damaging (including probably damaging missense, nonsense, and frameshift variants), which are associated to cardiovascular development. Each investigated patient showed at least one damaging variant in genes associated to cardiovascular development. These variants were further reduced by significance in cardiovascular development to 39 genetic variants (in 33 genes). Of note, a pair of siblings, both presenting with cardiac and renal defects, had the same damaging variant in two different genes.<\/jats:p>\n                  <jats:p>Conclusion\u2003Our results indicate a genetic background for congenital vascular disorders in patients with VACTERL association. In line with the literature, our data suggest that genetic mutation led to vascular diseases, which in turn may cause malformations similar to the VACTERL association.<\/jats:p>","DOI":"10.1055\/s-0041-1739423","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T18:42:43Z","timestamp":1637865763000},"page":"061-066","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Evidence for Congenital Vascular Disorders in Patients with VACTERL Association"],"prefix":"10.1055","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7106-7518","authenticated-orcid":false,"given":"Jessica","family":"Ritter","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Munich University Hospital, Munich, Germany"},{"name":"Department of Diagnostic and Interventional Radiology, Hospital Rechts der Isar, Technical University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Lisec","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Munich University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Heinrich","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Munich University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"von Schweinitz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Munich University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Kappler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Munich University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Hubertus","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, University Hospital of the Ruhr University Bochum, Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"issue":"05","key":"ref1","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1542\/peds.71.5.815","article-title":"A population study of the VACTERL association: evidence for its etiologic heterogeneity","volume":"71","author":"M J Khoury","year":"1983","journal-title":"Pediatrics"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/BF00441773","article-title":"An aetiological study of the VACTERL-association","volume":"144","author":"A Czeizel","year":"1985","journal-title":"Eur J Pediatr"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1750-1172-6-56","article-title":"VACTERL\/VATER association","volume":"6","author":"B D Solomon","year":"2011","journal-title":"Orphanet J Rare Dis"},{"issue":"12","key":"ref4","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1002\/ajmg.a.35638","article-title":"Clinical geneticists' views of VACTERL\/VATER association","volume":"158A","author":"B D Solomon","year":"2012","journal-title":"Am J Med Genet A"},{"issue":"01","key":"ref5","first-page":"104","article-title":"The VATER association. Vertebral defects, anal atresia, T-E fistula with esophageal atresia, radial and renal dysplasia: a spectrum of associated defects","volume":"82","author":"L Quan","year":"1973","journal-title":"J Pediatr"},{"issue":"03","key":"ref6","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0022-3476(74)80113-7","article-title":"Extending the scope of the VATER association: definition of the VATER syndrome","volume":"85","author":"S A Temtamy","year":"1974","journal-title":"J Pediatr"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1080\/00039896.1975.10666626","article-title":"A syndrome of multiple congenital anomalies associated with teratogenic exposure","volume":"30","author":"A H Nora","year":"1975","journal-title":"Arch Environ Health"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1159\/000346192","article-title":"Considering the embryopathogenesis of VACTERL association","volume":"4","author":"R E Stevenson","year":"2013","journal-title":"Mol Syndromol"},{"issue":"03","key":"ref9","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ijcard.2006.12.020","article-title":"Left superior vena cava in pediatric cardiology associated with extra-cardiac anomalies","volume":"123","author":"P G Postema","year":"2008","journal-title":"Int J Cardiol"},{"issue":"05","key":"ref10","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S0022-3476(82)80342-9","article-title":"Vascular pathogenesis of limb defects. I. Radial artery anatomy in radial aplasia","volume":"101","author":"M I Van Allen","year":"1982","journal-title":"J Pediatr"},{"issue":"03","key":"ref11","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/0002-9378(70)90422-9","article-title":"Genesis of single umbilical artery","volume":"108","author":"I W Monie","year":"1970","journal-title":"Am J Obstet Gynecol"},{"issue":"04","key":"ref12","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"I A Adzhubei","year":"2010","journal-title":"Nat Methods"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"K J Karczewski","year":"2020","journal-title":"Nature"},{"issue":"01","key":"ref14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"W Huang","year":"2009","journal-title":"Nucleic Acids Res"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"W Huang","year":"2009","journal-title":"Nat Protoc"},{"issue":"01","key":"ref16","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"M Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"D330","DOI":"10.1093\/nar\/gky1055","article-title":"The Gene Ontology Resource: 20 years and still GOing strong","volume":"47","author":"The Gene Ontology Consortium","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"03","key":"ref18","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1542\/peds.78.3.451","article-title":"Vascular steal: the pathogenetic mechanism producing sirenomelia and associated defects of the viscera and soft tissues","volume":"78","author":"R E Stevenson","year":"1986","journal-title":"Pediatrics"},{"issue":"01","key":"ref19","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1542\/peds.80.1.102","article-title":"Vascular basis for neural tube defects: a hypothesis","volume":"80","author":"R E Stevenson","year":"1987","journal-title":"Pediatrics"},{"issue":"02","key":"ref20","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/S0002-9149(01)02214-7","article-title":"Incidence of patent ductus arteriosus and patent foramen ovale in normal infants","volume":"89","author":"D Connuck","year":"2002","journal-title":"Am J Cardiol"},{"issue":"03","key":"ref21","doi-asserted-by":"crossref","first-page":"a028191","DOI":"10.1101\/cshperspect.a028191","article-title":"Ciliopathies","volume":"9","author":"D A Braun","year":"2017","journal-title":"Cold Spring Harb Perspect Biol"}],"container-title":["European Journal of Pediatric Surgery"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0041-1739423.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T19:07:24Z","timestamp":1645643244000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1739423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,25]]},"references-count":21,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2022,2,23]]},"published-print":{"date-parts":[[2022,2]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0041-1739423","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0939-7248","1439-359X"],"issn-type":[{"value":"0939-7248","type":"print"},{"value":"1439-359X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,25]]}}}