{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:57:38Z","timestamp":1788897458552,"version":"build-2803163510"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              1p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor\n              <jats:italic>PRDM16<\/jats:italic>\n              . Early studies suggest that deletion of\n              <jats:italic>PRDM16<\/jats:italic>\n              may underlie cardiomyopathy in patients with 1p36 deletion; however, the prognostic impact of\n              <jats:italic>PRDM16<\/jats:italic>\n              loss is unknown.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              This retrospective cohort included subjects with 1p36 deletion syndrome from 4 hospitals. Prevalence of cardiomyopathy and freedom from death, cardiac transplantation, or ventricular assist device were analyzed. A systematic review cohort was derived for further analysis. A cardiac-specific\n              <jats:italic>Prdm16<\/jats:italic>\n              knockout mouse (\n              <jats:italic>Prdm16<\/jats:italic>\n              conditional knockout) was generated. Echocardiography was performed at 4 and 6 to 7 months. Histology staining and qPCR were performed at 7 months to assess fibrosis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              The retrospective cohort included 71 patients. Among individuals with\n              <jats:italic>PRDM16<\/jats:italic>\n              deleted, 34.5% developed cardiomyopathy versus 7.7% of individuals with\n              <jats:italic>PRDM16<\/jats:italic>\n              not deleted (\n              <jats:italic>P<\/jats:italic>\n              =0.1). In the combined retrospective and systematic review cohort (n=134),\n              <jats:italic>PRDM16<\/jats:italic>\n              deletion-associated cardiomyopathy risk was recapitulated and significant (29.1% versus 10.8%,\n              <jats:italic>P<\/jats:italic>\n              =0.03).\n              <jats:italic>PRDM16<\/jats:italic>\n              deletion was associated with increased risk of death, cardiac transplant, or ventricular assist device (\n              <jats:italic>P<\/jats:italic>\n              =0.04). Among those\n              <jats:italic>PRDM16<\/jats:italic>\n              deleted, 34.5% of females developed cardiomyopathy versus 16.7% of their male counterparts (\n              <jats:italic>P<\/jats:italic>\n              =0.2). We find sex-specific differences in the incidence and the severity of contractile dysfunction and fibrosis in female\n              <jats:italic>Prdm16<\/jats:italic>\n              conditional knockout mice. Further, female\n              <jats:italic>Prdm16<\/jats:italic>\n              conditional knockout mice demonstrate significantly elevated risk of mortality (\n              <jats:italic>P<\/jats:italic>\n              =0.0003).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              <jats:italic>PRDM16<\/jats:italic>\n              deletion is associated with a significantly increased risk of cardiomyopathy and cardiac mortality.\n              <jats:italic>Prdm16<\/jats:italic>\n              conditional knockout mice develop cardiomyopathy in a sex-biased way. Patients with\n              <jats:italic>PRDM16<\/jats:italic>\n              deletion should be assessed for cardiac disease.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.122.003912","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T09:00:54Z","timestamp":1688374854000},"page":"390-400","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["<i>PRDM16<\/i>\n            Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study"],"prefix":"10.1161","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3308-2586","authenticated-orcid":true,"given":"Ryan J.","family":"Kramer","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology (R.J.K., A.C., B.S., L.E.P., M.B.R., K.B.P., K.M., S.L.A., A.P.L.), Duke University School of Medicine, Durham, NC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6531-7920","authenticated-orcid":true,"given":"Amir Nima","family":"Fatahian","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Integrative Physiology (A.N.F., O.M.T.R., M.A.H., S.B.), University of Utah, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology (R.J.K., A.C., B.S., L.E.P., M.B.R., K.B.P., K.M., S.L.A., A.P.L.), Duke University School of Medicine, Durham, NC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery","family":"Mortenson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, University of Tennessee Health Science Center, Memphis (J.M., J.O., H.R.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Osher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, University of Tennessee Health Science Center, Memphis (J.M., J.O., H.R.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0388-1451","authenticated-orcid":true,"given":"Bo","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology (R.J.K., A.C., B.S., L.E.P., M.B.R., K.B.P., K.M., S.L.A., A.P.L.), Duke University School of Medicine, Durham, NC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology (R.J.K., A.C., B.S., L.E.P., M.B.R., K.B.P., K.M., S.L.A., A.P.L.), Duke University School of Medicine, Durham, NC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1927-7176","authenticated-orcid":true,"given":"Michael B.","family":"Rosamilia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology (R.J.K., A.C., B.S., L.E.P., M.B.R., K.B.P., K.M., S.L.A., A.P.L.), Duke University School of Medicine, Durham, NC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyra B.","family":"Potter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology (R.J.K., A.C., B.S., L.E.P., M.B.R., K.B.P., K.M., S.L.A., A.P.L.), Duke University School of Medicine, Durham, NC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaila","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology (R.J.K., A.C., B.S., L.E.P., M.B.R., K.B.P., K.M., S.L.A., A.P.L.), Duke University 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