{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T03:30:34Z","timestamp":1771558234475,"version":"3.50.1"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Inherited primary arrhythmia syndromes and arrhythmogenic cardiomyopathies can lead to sudden cardiac arrest in otherwise healthy individuals. The burden and expression of these diseases in a real-world, well-phenotyped cardiovascular population is not well understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Whole exome sequencing was performed on 8574 individuals from the CATHGEN cohort (Catheterization Genetics). Variants in 55 arrhythmia-related genes (associated with 8 disorders) were identified and assessed for pathogenicity based on American College of Genetics and Genomics\/Association for Molecular Pathology criteria. Individuals carrying pathogenic\/likely pathogenic (P\/LP) variants were grouped by arrhythmogenic disorder and matched 1:5 to noncarrier controls based on age, sex, and genetic ancestry. Long-term phenotypic data were annotated through deep electronic health record review.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Fifty-eight P\/LP variants were found in 79 individuals in 12 genes associated with 5 arrhythmogenic disorders (arrhythmogenic right ventricular cardiomyopathy, Brugada syndrome, hypertrophic cardiomyopathy,\n              <jats:italic>LMNA<\/jats:italic>\n              -related cardiomyopathy, and long QT syndrome). The penetrance of these P\/LP variants in this cardiovascular cohort was 33%, 0%, 28%, 83%, and 4%, respectively. Carriers of P\/LP variants associated with arrhythmogenic disorders showed significant differences in ECG, imaging, and clinical phenotypes compared with noncarriers, but displayed no difference in survival. Carriers of novel truncating variants in\n              <jats:italic>FLNC, MYBPC3<\/jats:italic>\n              , and\n              <jats:italic>MYH7<\/jats:italic>\n              also developed relevant arrhythmogenic cardiomyopathy phenotypes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              In a real-world cardiovascular cohort, P\/LP variants in arrhythmia-related genes were relatively common (1:108 prevalence) and most penetrant in\n              <jats:italic>LMNA<\/jats:italic>\n              . While hypertrophic cardiomyopathy P\/LP variant carriers showed significant differences in clinical outcomes compared with noncarriers, carriers of P\/LP variants associated with other arrhythmogenic disorders displayed only ECG differences.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.121.003675","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T15:45:04Z","timestamp":1663861504000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Prevalence and Phenotypic Burden of Monogenic Arrhythmias Using Integration of Electronic Health Records With Genetics"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0706-9548","authenticated-orcid":true,"given":"Navid A.","family":"Nafissi","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine (N.A.N., A.C.C., W.E.K., J.P.P., J.P.D., A.Y.S., S.H.S.), 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