{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T06:15:43Z","timestamp":1696659343470},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T00:00:00Z","timestamp":1438819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY019267"],"award-info":[{"award-number":["EY019267"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:label \/><jats:p>Congenital heart malformations, including those of the great vessels, are among the most common human birth defects. The goal of this study was to identify the significance of a de novo mosaic <jats:italic>PTPN12<\/jats:italic> partial deletion identified in a newborn with an interrupted aortic arch type A, ventricular septal defect, and pyloric stenosis. <jats:italic>PTPN12<\/jats:italic>, a downstream target of the RAS pathway, has a known role in endothelial cell adhesion and migration. Neither genetic nor genomic variants in <jats:italic>PTPN12<\/jats:italic> have been described in a human patient; therefore, we evaluated the effect of <jats:italic>ptpn12<\/jats:italic> in a mouse conditional knockout and zebrafish knockdown model to determine the significance of a loss in gene expression. Observed loss of <jats:italic>ptpn12<\/jats:italic> expression in zebrafish resulted in abnormal branchial arch and tail vasculature patterns, with reduced blood flow throughout the animal. This phenotype was supported by anomalous vasculature in a conditional <jats:italic>Ptpn12<\/jats:italic> mouse knockout. Given the novel co\u2010occurrence of interrupted aortic arch type A, ventricular septal defect, and partial deletion of <jats:italic>PTPN12<\/jats:italic> in the patient, as well as vascular phenotypes in <jats:italic>Ptpn12<\/jats:italic> mouse and <jats:italic>ptpn12<\/jats:italic> zebrafish models, it is likely that <jats:italic>PTPN12<\/jats:italic> has a significant role in cardiovascular development and vessel formation during human embryonic development. Furthermore, the partial deletion of <jats:italic>PTPN12<\/jats:italic> lead to interrupted aortic arch type A in this child and may represent a novel condition caused by a null mutation in the RAS pathway. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37279","type":"journal-article","created":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T19:48:31Z","timestamp":1438890511000},"page":"2674-2683","source":"Crossref","is-referenced-by-count":3,"title":["Mosaic partial deletion of <i>PTPN12<\/i> in a child with interrupted aortic arch type A"],"prefix":"10.1002","volume":"167","author":[{"given":"Elizabeth A.","family":"Duffy","sequence":"first","affiliation":[{"name":"Division of Genetics and Metabolism Department of Pediatrics University of Minnesota Minneapolis Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela R.","family":"Pretorius","sequence":"additional","affiliation":[{"name":"Division of Genetics and 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