{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T09:28:13Z","timestamp":1784366893374,"version":"3.55.0"},"reference-count":43,"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>Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by fibrofatty replacement of the right and left ventricle, often causing ventricular dysfunction and life-threatening arrhythmias. Variants in desmosomal genes account for up to 60% of cases. Our objective was to establish the prevalence and clinical features of ACM stemming from pathogenic variants in the nondesmosomal cadherin 2 (CDH2), a novel genetic substrate of ACM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              A cohort of 500 unrelated patients with a definite diagnosis of ACM and no disease-causing variants in the main ACM genes was assembled. Genetic screening of\n              <jats:italic>CDH2<\/jats:italic>\n              was performed through next-generation or Sanger sequencing. Whenever possible, cascade screening was initiated in the families of\n              <jats:italic>CDH2<\/jats:italic>\n              -positive probands, and clinical evaluation was performed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Genetic screening of\n              <jats:italic>CDH2<\/jats:italic>\n              led to the identification of 7 rare variants: 5, identified in 6 probands, were classified as pathogenic or likely pathogenic. The previously established p.D407N pathogenic variant was detected in 2 additional probands. Probands and family members with pathogenic\/likely pathogenic variants in\n              <jats:italic>CDH2<\/jats:italic>\n              were clinically evaluated, and along with previously published cases, altogether contributed to the identification of gene-specific features (13 cases from this cohort and 11 previously published, for a total of 9 probands and 15 family members). Ventricular arrhythmic events occurred in most\n              <jats:italic>CDH2<\/jats:italic>\n              -positive subjects (20\/24, 83%), while the occurrence of heart failure was rare (2\/24, 8.3%). Among probands, sustained ventricular tachycardia and sudden cardiac death occurred in 5\/9 (56%).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              In this worldwide cohort of previously genotype-negative ACM patients, the prevalence of probands with\n              <jats:italic>CDH2<\/jats:italic>\n              pathogenic\/likely pathogenic variants was 1.2% (6\/500). Our data show that this cohort of\n              <jats:italic>CDH2<\/jats:italic>\n              -ACM patients has a high incidence of ventricular arrhythmias, while evolution toward heart failure is rare.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.120.003097","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T19:49:39Z","timestamp":1612986579000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Cadherin 2-Related Arrhythmogenic Cardiomyopathy"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3435-9823","authenticated-orcid":true,"given":"Alice","family":"Ghidoni","sequence":"first","affiliation":[{"name":"Center for Cardiac Arrhythmias of Genetic Origin (A.G., M.-C.K., P.J.S., L.C.), Istituto Auxologico Italiano, IRCCS, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3383-3984","authenticated-orcid":true,"given":"Perry M.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Center for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, United Kingdom (P.M.E., P.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2363-8758","authenticated-orcid":true,"given":"Petros","family":"Syrris","sequence":"additional","affiliation":[{"name":"Center for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, United Kingdom (P.M.E., P.S.)."}],"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 University, Baltimore, 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