{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:57:36Z","timestamp":1788897456967,"version":"build-2803163510"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Less than 40% of patients with dilated cardiomyopathy (DCM) have a pathogenic\/likely pathogenic genetic variant identified.\n              <jats:italic toggle=\"yes\">TBX20<\/jats:italic>\n              has been linked to congenital heart defects; although an association with left ventricular noncompaction (LVNC) and DCM has been proposed, it is still considered a gene with limited evidence for these phenotypes. This study sought to investigate the association between the\n              <jats:italic toggle=\"yes\">TBX20<\/jats:italic>\n              truncating variant (\n              <jats:italic toggle=\"yes\">TBX20tv<\/jats:italic>\n              ) and DCM\/LVNC.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              <jats:italic toggle=\"yes\">TBX20<\/jats:italic>\n              was sequenced by next-generation sequencing in 7463 unrelated probands with a diagnosis of DCM or LVNC, 22\u2005773 probands of an internal comparison group (hypertrophic cardiomyopathy, channelopathies, or aortic diseases), and 124\u2005098 external controls (individuals from the gnomAD database). Enrichment of\n              <jats:italic toggle=\"yes\">TBX20tv<\/jats:italic>\n              in DCM\/LVNC was calculated, cosegregation was determined in selected families, and clinical characteristics and outcomes were analyzed in carriers.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              <jats:italic toggle=\"yes\">TBX20tv<\/jats:italic>\n              was enriched in DCM\/LVNC (24\/7463; 0.32%) compared with internal (1\/22\u2005773; 0.004%) and external comparison groups (4\/124\u2005098; 0.003%), with odds ratios of 73.23 (95% CI, 9.90\u2013541.45;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.0001) and 99.76 (95% CI, 34.60\u2013287.62;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.0001), respectively.\n              <jats:italic toggle=\"yes\">TBX20tv<\/jats:italic>\n              was cosegregated with DCM\/LVNC phenotype in 21 families for a combined logarythm of the odds score of 4.53 (strong linkage). Among 57 individuals with\n              <jats:italic toggle=\"yes\">TBX20tv<\/jats:italic>\n              (49.1% men; mean age, 35.9\u00b120.8 years), 41 (71.9%) exhibited DCM\/LVNC, of whom 14 (34.1%) had also congenital heart defects. After a median follow-up of 6.9 (95% CI, 25\u201375:3.6\u201314.5) years, 9.7% of patients with DCM\/LVNC had end-stage heart failure events and 4.8% experienced malignant ventricular arrhythmias.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              <jats:italic toggle=\"yes\">TBX20tv<\/jats:italic>\n              is associated with DCM\/LVNC; congenital heart defect is also present in around one-third of cases.\n              <jats:italic toggle=\"yes\">TBX20tv<\/jats:italic>\n              -associated DCM\/LVNC is characterized by a nonaggressive phenotype, with a low incidence of major cardiovascular events.\n              <jats:italic toggle=\"yes\">TBX20<\/jats:italic>\n              should be considered a definitive gene for DCM and LVNC and routinely included in genetic testing panels for these phenotypes.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.123.004404","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T10:00:22Z","timestamp":1707904822000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Role of\n            <i>TBX20<\/i>\n            Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction"],"prefix":"10.1161","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0420-8207","authenticated-orcid":true,"given":"Almudena","family":"Amor-Salamanca","sequence":"first","affiliation":[{"name":"Cardiology Department, Health in Code SL, A Coru\u00f1a, Spain (A.A.-S., L.d.l.H.R., I.C.-R., S.G.-H., M.V.-G., I.G.-D., J.P.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Santana Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain (A.S.R., L.M.G.-C.)."},{"name":"Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Spain (A.S.R., L.M.G.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4918-5304","authenticated-orcid":true,"given":"Hazhee","family":"Rasoul","sequence":"additional","affiliation":[{"name":"Inherited Cardiovascular Diseases Unit, St. Bartholomew\u2019s Hospital, Barts Health NHS Trust, London, United Kingdom (H.R., K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 F.","family":"Rodr\u00edguez-Palomares","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Unit and Inherited Cardiac Diseases Unit, Cardiology Department, Vall d\u2032Hebron University Hospital, Barcelona, Spain (J.F.R.-P., J.L.F.)."},{"name":"Vall d\u2032Hebron Rsrch Unit, Barcelona, Spain (J.F.R.-P.)."},{"name":"Universitat Aut\u00f2noma Barcelona, Spain (J.F.R.-P., J.P.T.-Q.)."},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain (J.F.R.-P., M.G.D., J.M.G.-P., J.R.G.-B., P.G.-P.)."},{"name":"European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, The Netherlands (J.F.R.-P., J.L.F., J.R.G.-B., P.G.-P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0274-4313","authenticated-orcid":true,"given":"Oana","family":"Moldovan","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica, Department de Pediatria, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, Portugal (O.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0262-7774","authenticated-orcid":true,"given":"Thomas Morris","family":"Hey","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Clinic of Inherited Cardiovascular Diseases, Odense University Hospital, Denmark (T.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0726-9646","authenticated-orcid":true,"given":"Mar\u00eda Gallego","family":"Delgado","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain (J.F.R.-P., M.G.D., J.M.G.-P., J.R.G.-B., P.G.-P.)."},{"name":"Cardiology Department, Hospital Universitario de Salamanca, Spain (M.G.D.)."},{"name":"Biomedical Research Institute of Salamanca, Gerencia Regional de Salud de Castilla y Le\u00f3n, Spain (M.G.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3031-8768","authenticated-orcid":true,"given":"David L\u00f3pez","family":"Cuenca","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Inherited Cardiac Diseases Unit, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, Murcia, Spain (D.L.C., J.R.G.-B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1975-9132","authenticated-orcid":true,"given":"Daniel","family":"de Castro Campos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Failure and Inherited Cardiac Diseases Unit, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain (D.d.C.C., P.G.-P., J.P.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8689-0301","authenticated-orcid":true,"given":"Mar\u00eda Teresa","family":"Basurte-Elorz","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Complejo Hospitalario de Navarra, Pamplona, Spain 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