{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:52:57Z","timestamp":1792637577028,"version":"4.5.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The causes of cardiomyopathy in children are less well described than in adults. We evaluated the clinical diagnoses and genetic causes of childhood cardiomyopathy and outcomes of cascade genetic testing in family members.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We recruited children from a pediatric cardiology service or genetic heart diseases clinic. We performed Sanger, gene panel, exome or genome sequencing and classified variants for pathogenicity using American College of Molecular Genetics and Genomics guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Cardiomyopathy was diagnosed in 221 unrelated children aged \u226418 years. Children mostly had hypertrophic cardiomyopathy (n=98, 44%) or dilated cardiomyopathy (n=89, 40%). The highest genetic testing diagnostic yields were in restrictive cardiomyopathy (n=16, 80%) and hypertrophic cardiomyopathy (n=65, 66%), and lowest in dilated cardiomyopathy (n=26, 29%) and left ventricular noncompaction (n=3, 25%). Pathogenic variants were primarily found in genes encoding sarcomere proteins, with\n                      <jats:italic toggle=\"yes\">TNNT2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TNNI3<\/jats:italic>\n                      variants associated with more severe clinical outcomes. Ten children (4.5%) had multiple pathogenic variants. Genetic test results prompted review of clinical diagnosis in 14 families with syndromic, mitochondrial or metabolic gene variants. Cascade genetic testing in 127 families confirmed 24 de novo variants, recessive inheritance in 8 families, and supported reclassification of 12 variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Genetic testing of children with cardiomyopathy supports a precise clinical diagnosis, which may inform prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.121.003686","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T14:14:32Z","timestamp":1665670472000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Genetic Basis of Childhood Cardiomyopathy"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-9864","authenticated-orcid":true,"given":"Richard D.","family":"Bagnall","sequence":"first","affiliation":[{"name":"Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., N.N., J.I., J.C., C.S.)."},{"name":"Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., J.I., J.C., C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0264-3395","authenticated-orcid":true,"given":"Emma S.","family":"Singer","sequence":"additional","affiliation":[{"name":"Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., N.N., J.I., J.C., C.S.)."},{"name":"Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., J.I., J.C., C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5408-1107","authenticated-orcid":true,"given":"Julie","family":"Wacker","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Royal Children\u2019s Hospital, Melbourne, VIC, Australia; (J.W., R.G.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7259-394X","authenticated-orcid":true,"given":"Natalie","family":"Nowak","sequence":"additional","affiliation":[{"name":"Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., N.N., J.I., J.C., C.S.)."},{"name":"Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia (N.N., J.I., C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4846-7676","authenticated-orcid":true,"given":"Jodie","family":"Ingles","sequence":"additional","affiliation":[{"name":"Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., N.N., J.I., J.C., C.S.)."},{"name":"Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., J.I., J.C., C.S.)."},{"name":"Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia (N.N., J.I., C.S.)."},{"name":"Centre for Population Genomics, Garvan Institute of Medical Research, and UNSW, Sydney, NSW, Australia (J.I.)."},{"name":"Murdoch Children\u2019s Research Institute, Melbourne, VIC, Australia (J.I., I.K., I.M., R.G.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3970-9186","authenticated-orcid":true,"given":"Ingrid","family":"King","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, Melbourne, VIC, Australia (J.I., I.K., I.M., R.G.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-8542","authenticated-orcid":true,"given":"Ivan","family":"Macciocca","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, Melbourne, VIC, Australia (J.I., I.K., I.M., R.G.W.)."},{"name":"University of Melbourne, Melbourne, VIC, Australia (I.M., R.G.W.)."},{"name":"Victorian Clinical Genetics Services, Melbourne, VIC, Australia (I.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Crowe","sequence":"additional","affiliation":[{"name":"Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., N.N., J.I., J.C., C.S.)."},{"name":"Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., J.I., J.C., C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-0293","authenticated-orcid":true,"given":"Anne","family":"Ronan","sequence":"additional","affiliation":[{"name":"Hunter Genetics Unit (A.R.)."},{"name":"University of Newcastle, Newcastle, NSW, Australia (A.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7324-8697","authenticated-orcid":true,"given":"Robert G.","family":"Weintraub","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Royal Children\u2019s Hospital, Melbourne, VIC, Australia; (J.W., R.G.W.)."},{"name":"Murdoch Children\u2019s Research Institute, Melbourne, VIC, Australia (J.I., I.K., I.M., R.G.W.)."},{"name":"University of Melbourne, Melbourne, VIC, Australia (I.M., R.G.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6441-274X","authenticated-orcid":true,"given":"Christopher","family":"Semsarian","sequence":"additional","affiliation":[{"name":"Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., N.N., J.I., J.C., C.S.)."},{"name":"Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia (R.D.B., E.S.S., J.I., J.C., C.S.)."},{"name":"Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia (N.N., J.I., C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000682"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab148"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-017-1779-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx596"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.12.071"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13024"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.017731"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.016195"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.08.2171"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.120.002969"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31764"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-00970-5"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa075463"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13812"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22942"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.90"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.118.002368"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.078"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.120.003250"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2021-107774"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.120.002929"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.120.003117"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.205"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1510687"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001666"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.218"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021737"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"}],"container-title":["Circulation: Genomic and Precision Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGEN.121.003686","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T14:56:58Z","timestamp":1774364218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGEN.121.003686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1161\/CIRCGEN.121.003686"],"URL":"https:\/\/doi.org\/10.1161\/circgen.121.003686","relation":{},"ISSN":["2574-8300"],"issn-type":[{"value":"2574-8300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12]]},"assertion":[{"value":"2021-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}