{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:36:42Z","timestamp":1780472202486,"version":"3.54.1"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Genomic screening holds great promise for presymptomatic identification of hidden disease, and prevention of dramatic events, including sudden cardiac death associated with arrhythmogenic cardiomyopathy (ACM). Herein, we present findings from clinical follow-up of carriers of ACM-associated pathogenic\/likely pathogenic desmosome variants ascertained through genomic screening.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Of 64 548 eligible participants in Geisinger MyCode Genomic Screening and Counseling program (2015\u2013present), 92 individuals (0.14%) identified with pathogenic\/likely pathogenic desmosome variants by clinical laboratory testing were referred for evaluation. We reviewed preresult medical history, patient-reported family history, and diagnostic testing results to assess both arrhythmogenic right ventricular cardiomyopathy and left-dominant ACM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              One carrier had a prior diagnosis of dilated cardiomyopathy with arrhythmia; no other related diagnoses or diagnostic family history criteria were reported. Fifty-nine carriers (64%) had diagnostic testing in follow-up. Excluding the variant, 21\/59 carriers satisfied at least one arrhythmogenic right ventricular cardiomyopathy task force criterion, 11 (52%) of whom harbored\n              <jats:italic>DSP<\/jats:italic>\n              variants, but only 5 exhibited multiple criteria. Six (10%) carriers demonstrated evidence of left-dominant ACM, including high rates of atypical late gadolinium enhancement by magnetic resonance imaging and nonsustained ventricular tachycardia. Two individuals received new cardiomyopathy diagnoses and received defibrillators for primary prevention.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Genomic screening for pathogenic\/likely pathogenic variants in desmosome genes can uncover both left- and right-dominant ACM. Findings of overt cardiomyopathy were limited but were most common in\n              <jats:italic>DSP<\/jats:italic>\n              -variant carriers and notably absent in\n              <jats:italic>PKP2<\/jats:italic>\n              -variant carriers. Consideration of the pathogenic\/likely pathogenic variant as a major criterion for diagnosis is inappropriate in the setting of genomic screening.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.120.003302","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:08Z","timestamp":1615248008000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Clinical Findings and Diagnostic Yield of Arrhythmogenic Cardiomyopathy Through Genomic Screening of Pathogenic or Likely Pathogenic Desmosome Gene Variants"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8184-8676","authenticated-orcid":true,"given":"Eric D.","family":"Carruth","sequence":"first","affiliation":[{"name":"Department of Translational Data Science and Informatics (E.D.C., C.D.N., B.K.F., C.M.H.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Beer","sequence":"additional","affiliation":[{"name":"The Heart Institute (D.B., A.A., M.E.M., B.K.F., A.C.S., C.M.H.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6466-2615","authenticated-orcid":true,"given":"Amro","family":"Alsaid","sequence":"additional","affiliation":[{"name":"The Heart Institute (D.B., A.A., M.E.M., B.K.F., A.C.S., C.M.H.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7643-0862","authenticated-orcid":true,"given":"Marci L.B.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute (M.L.B.S., M.M., M.A.K., A.H.B., A.C.S.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"McMinn","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute (M.L.B.S., M.M., M.A.K., A.H.B., A.C.S.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4708-2261","authenticated-orcid":true,"given":"Melissa A.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute (M.L.B.S., M.M., M.A.K., A.H.B., A.C.S.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6518-2453","authenticated-orcid":true,"given":"Adam H.","family":"Buchanan","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute (M.L.B.S., M.M., M.A.K., A.H.B., A.C.S.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Nevius","sequence":"additional","affiliation":[{"name":"Department of Translational Data Science and Informatics (E.D.C., C.D.N., B.K.F., C.M.H.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9262-9433","authenticated-orcid":true,"given":"Hugh","family":"Calkins","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Center, Baltimore, MD (H.C., C.A.J., B.M., C.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8040-4600","authenticated-orcid":true,"given":"Cynthia A.","family":"James","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Center, Baltimore, MD (H.C., C.A.J., B.M., C.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7870-8584","authenticated-orcid":true,"given":"Brittney","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Center, Baltimore, MD (H.C., C.A.J., B.M., C.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Tichnell","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Center, Baltimore, MD (H.C., C.A.J., B.M., C.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-0978","authenticated-orcid":true,"given":"Martin E.","family":"Matsumura","sequence":"additional","affiliation":[{"name":"The Heart Institute (D.B., A.A., M.E.M., B.K.F., A.C.S., C.M.H.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2557-6749","authenticated-orcid":true,"given":"H. Lester","family":"Kirchner","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences (H.L.K.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6231-9442","authenticated-orcid":true,"given":"Brandon K.","family":"Fornwalt","sequence":"additional","affiliation":[{"name":"Department of Translational Data Science and Informatics (E.D.C., C.D.N., B.K.F., C.M.H.), Geisinger, Danville, PA."},{"name":"The Heart Institute (D.B., A.A., M.E.M., B.K.F., A.C.S., C.M.H.), Geisinger, Danville, PA."},{"name":"Department of Radiology (B.K.F.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-7786","authenticated-orcid":true,"given":"Amy C.","family":"Sturm","sequence":"additional","affiliation":[{"name":"The Heart Institute (D.B., A.A., M.E.M., B.K.F., A.C.S., C.M.H.), Geisinger, Danville, PA."},{"name":"Genomic Medicine Institute (M.L.B.S., M.M., M.A.K., A.H.B., A.C.S.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3227-4490","authenticated-orcid":true,"given":"Christopher M.","family":"Haggerty","sequence":"additional","affiliation":[{"name":"Department of Translational Data Science and Informatics (E.D.C., C.D.N., B.K.F., C.M.H.), Geisinger, Danville, PA."},{"name":"The Heart Institute (D.B., A.A., M.E.M., B.K.F., A.C.S., C.M.H.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.101"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2011.78"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.190"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2019.05.007"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.542266"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2016.01.026"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198801213180301"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.119.002579"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.90"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.40"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.840827"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.09.019"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.187"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6814"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.03.012"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.07.009"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_6_19_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing.","volume":"57","author":"Benjamini Y","year":"1995","unstructured":"Benjamini, Y, Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B. 1995;57:289\u2013300.","journal-title":"J R Stat Soc Ser B"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.184.5.01841420"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.044934"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2020.06.005"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.05.022"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.114.001003"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.06.033"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2018.05.017"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046020"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.043504"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu509"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2013.105"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu301"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2017.02.013"}],"container-title":["Circulation: Genomic and Precision Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGEN.120.003302","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:39:50Z","timestamp":1715564390000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGEN.120.003302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1161\/CIRCGEN.120.003302"],"URL":"https:\/\/doi.org\/10.1161\/circgen.120.003302","relation":{},"ISSN":["2574-8300"],"issn-type":[{"value":"2574-8300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4]]},"assertion":[{"value":"2020-08-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e003302"}}