{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T19:39:29Z","timestamp":1771529969886,"version":"3.50.1"},"reference-count":139,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T00:00:00Z","timestamp":1633824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Tracheoesophageal Fistula (TOF) is a congenital anomaly for which the cause is unknown in the majority of patients. OA\/TOF is a variable feature in many (often mono-) genetic syndromes. Research using animal models targeting genes involved in candidate pathways often result in tracheoesophageal phenotypes. However, there is limited overlap in the genes implicated by animal models and those found in OA\/TOF-related syndromic anomalies. Knowledge on affected pathways in animal models is accumulating, but our understanding on these pathways in patients lags behind. If an affected pathway is associated with both animals and patients, the mechanisms linking the genetic mutation, affected cell types or cellular defect, and the phenotype are often not well understood. The locus heterogeneity and the uncertainty of the exact heritability of OA\/TOF results in a relative low diagnostic yield. OA\/TOF is a sporadic finding with a low familial recurrence rate. As parents are usually unaffected, de novo dominant mutations seems to be a plausible explanation. The survival rates of patients born with OA\/TOF have increased substantially and these patients start families; thus, the detection and a proper interpretation of these dominant inherited pathogenic variants are of great importance for these patients and for our understanding of OA\/TOF aetiology.<\/jats:p>","DOI":"10.3390\/genes12101595","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:23:25Z","timestamp":1633901005000},"page":"1595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Heritability and De Novo Mutations in Oesophageal Atresia and Tracheoesophageal Fistula Aetiology"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8235-4010","authenticated-orcid":false,"given":"Erwin","family":"Brosens","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children\u2019s Hospital, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rutger W. W.","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Center for Biomics, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannie","family":"Douben","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children\u2019s Hospital, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolande","family":"van Bever","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children\u2019s Hospital, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice S.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children\u2019s Hospital, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rene M. H.","family":"Wijnen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children\u2019s Hospital, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0421-8301","authenticated-orcid":false,"given":"Wilfred F. J.","family":"van IJcken","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Center for Biomics, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dick","family":"Tibboel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children\u2019s Hospital, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9291-4971","authenticated-orcid":false,"given":"Robbert J.","family":"Rottier","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Surgery & Cell Biology, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annelies","family":"de Klein","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children\u2019s Hospital, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00383-011-3014-1","article-title":"Aspects of esophageal atresia in a population-based setting: Incidence, mortality, and cancer risk","volume":"28","author":"Oddsberg","year":"2012","journal-title":"Pediatric Surg. 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