{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:46:21Z","timestamp":1787499981607,"version":"build-2736575974"},"reference-count":30,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Heart"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pathogenesis of transposition of the great arteries (TGA) is still largely unknown. In general, TGA is not associated with the more common genetic disorders nor with extracardiac anomalies, whereas it can be found in individuals with lateralisation defects, heterotaxy and asplenia syndrome (right isomerism).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To analyse genes previously associated with heterotaxy in order to assess mutations in familial TGA unassociated with other features of laterality defects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Probands of seven families with isolated TGA and a family history of concordant or discordant congenital heart disease were screened for mutations in the\n                      <jats:italic>ZIC3<\/jats:italic>\n                      ,\n                      <jats:italic>ACVR2B<\/jats:italic>\n                      ,\n                      <jats:italic>LEFTYA<\/jats:italic>\n                      ,\n                      <jats:italic>CFC1<\/jats:italic>\n                      ,\n                      <jats:italic>NODAL<\/jats:italic>\n                      ,\n                      <jats:italic>FOXH1<\/jats:italic>\n                      ,\n                      <jats:italic>GDF1<\/jats:italic>\n                      ,\n                      <jats:italic>CRELD1<\/jats:italic>\n                      ,\n                      <jats:italic>GATA4<\/jats:italic>\n                      and\n                      <jats:italic>NKX2.5<\/jats:italic>\n                      genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mutation analysis allowed the identification of three sequence variations in two out of seven TGA probands. A\n                      <jats:italic>FOXH1<\/jats:italic>\n                      (Pro21Ser) missense variant was found in a proband who was also heterozogous for an amino acid substitution (Gly17Cys) in the\n                      <jats:italic>ZIC3<\/jats:italic>\n                      gene. This\n                      <jats:italic>ZIC3<\/jats:italic>\n                      variant was also found in another family member with a second sequence variation (Val150Ile) in the\n                      <jats:italic>NKX2.5<\/jats:italic>\n                      gene homeodomain who was affected by multiple ventricular septal defects. A second proband was found to harbour a splice site variant (IVS2-1G\u2192C) in the\n                      <jats:italic>NODAL<\/jats:italic>\n                      gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present study provides evidence that some cases of familial TGA are caused by mutations in laterality genes and therefore are part of the same disease spectrum of heterotaxy syndrome, and argues for an oligogenic or complex mode of inheritance in these pedigrees.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/hrt.2009.181685","type":"journal-article","created":{"date-parts":[[2009,11,20]],"date-time":"2009-11-20T20:31:42Z","timestamp":1258749102000},"page":"673-677","source":"Crossref","is-referenced-by-count":120,"title":["Familial transposition of the great arteries caused by multiple mutations in laterality genes"],"prefix":"10.1136","volume":"96","author":[{"given":"Alessandro","family":"De Luca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sarkozy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Consoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosangela","family":"Ferese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Guida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lisa","family":"Dentici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Mingarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Bellacchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Tuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Limongelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Digilio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Marino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Dallapiccola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2009,11,20]]},"reference":[{"key":"2025092022211816000_96.9.673.1","unstructured":"Clark EB . Mechanism in the pathogenesis of congenital cardiac malformations. In: Pierpont ME Moller JH , eds. Genetics of cardiovascular disease. Boston: Martinus Nijhoff Publishing, 1986:3\u201311."},{"key":"2025092022211816000_96.9.673.2","unstructured":"Ferencz C Loffredo CA Correa-Villasenor A . Genetic and environmental risk factors of major cardiovascular malformations: the Baltimore\u2013Washington Infant Study, 1981\u20131989. Armonk, NY: Futura Publishing Company, 1997."},{"key":"2025092022211816000_96.9.673.3","doi-asserted-by":"publisher","DOI":"10.1161\/hc4701.099786"},{"key":"2025092022211816000_96.9.673.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2006.04.004"},{"key":"2025092022211816000_96.9.673.5","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(86)90256-0"},{"key":"2025092022211816000_96.9.673.6","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10376"},{"key":"2025092022211816000_96.9.673.7","doi-asserted-by":"crossref","unstructured":"Casey BKK . 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