{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:02:50Z","timestamp":1792782170347,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,9,26]],"date-time":"2014-09-26T00:00:00Z","timestamp":1411689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Health-e-Child Integrated Project","award":["IST-2004-027749"],"award-info":[{"award-number":["IST-2004-027749"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Tetralogy of Fallot (TOF) (OMIM #187500) is the most frequent conotruncal congenital heart defect (CHD) with a range of intra\u2010 and extracardiac phenotypes.\n                      <jats:italic>TBX5<\/jats:italic>\n                      is a transcription factor with well\u2010defined roles in heart and forelimb development, and mutations in\n                      <jats:italic>TBX5<\/jats:italic>\n                      are associated with Holt\u2013Oram syndrome (HOS) (OMIM#142900). Here we report on the screening of 94 TOF patients for mutations in\n                      <jats:italic>TBX5, NKX2.5<\/jats:italic>\n                      and\n                      <jats:italic>GATA4<\/jats:italic>\n                      genes. We identified two heterozygous mutations in\n                      <jats:italic>TBX5<\/jats:italic>\n                      . One mutation was detected in a Moroccan patient with TOF, a large ostium secundum atrial septal defect and complete atrioventricular block, and features of HOS including bilateral triphalangeal thumbs and fifth finger clinodactyly. This patient carried a previously described de novo, stop codon mutation (p.R279X) located in exon 8 causing a premature truncated protein. In a second patient from Italy with TOF, ostium secundum atrial septal defect and progressive arrhythmic changes on ECG, we identified a maternally inherited novel mutation in exon 9, which caused a substitution of a serine with a leucine at amino acid position 372 (p.S372L, c.1115C&gt;T). The mother's clinical evaluation demonstrated frequent ventricular extrasystoles and an atrial septal aneurysm. Physical examination and radiographs of the hands showed no apparent skeletal defects in either child or mother. Molecular evaluation of the p.S372L mutation demonstrated a gain\u2010of\u2010function phenotype. We also review the literature on the co\u2010occurrence of TOF and HOS, highlighting its relevance. This is the first systematic screening for\n                      <jats:italic>TBX5<\/jats:italic>\n                      mutations in TOF patients which detected mutations in two of 94 (2.1%) patients. \u00a9 2014 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajmg.a.36783","type":"journal-article","created":{"date-parts":[[2014,9,26]],"date-time":"2014-09-26T15:25:59Z","timestamp":1411745159000},"page":"3100-3107","source":"Crossref","is-referenced-by-count":51,"title":["Identification of\n                    <i>TBX5<\/i>\n                    mutations in a series of 94 patients with Tetralogy of Fallot"],"prefix":"10.1002","volume":"164","author":[{"given":"Anwar","family":"Baban","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiology and Cardiosurgery Bambino Ges\u00f9 Children Hospital IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex Vincent","family":"Postma","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Embryology and Physiology Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Marini","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics Gaslini Children Hospital Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Trocchio","sequence":"additional","affiliation":[{"name":"Cardiovascular and Cardiosurgical Department Gaslini Children Hospital Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Santilli","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Cardiosurgery Bambino Ges\u00f9 Children Hospital IRCCS Rome 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"Barnett","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Embryology and Physiology Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis Job","family":"Boogerd","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Embryology and Physiology Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Dallapiccola","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Cytogenetics Bambino Ges\u00f9 Children Hospital IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Digilio","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Cytogenetics Bambino Ges\u00f9 Children Hospital IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Ravazzolo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics Gaslini Children Hospital Genoa Italy"},{"name":"Department of Pediatrics and Center of Excellence for Biomedical Research (CEBR) University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Pongiglione","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Cardiosurgery Bambino Ges\u00f9 Children Hospital IRCCS Rome 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