{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:31:14Z","timestamp":1785324674689,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005640","name":"Faculdade de Medicina da Universidade de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005640","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Mutations in the <jats:bold>Lamin A\/C<\/jats:bold><jats:italic>(LMNA<\/jats:italic>) gene are commonly associated with cardiac manifestations, such as dilated cardiomyopathy (DCM) and conduction system disease. However, the overall spectrum and penetrance of rare <jats:italic>LMNA<\/jats:italic> variants are unknown. The present study described the presence of <jats:italic>LMNA<\/jats:italic><jats:bold>variants<\/jats:bold> in patients with \u201clone atrial fibrillation (AF)\u201d as their sole clinical presentation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>One-hundred and one consecutive patients with \u201clone AF\u201d criteria were initially screened by genetic testing. Genetic variants were classified according to the American College of Genetic and Genomic criteria. All subjects were evaluated through clinical and familial history, ECG, 24-h Holter monitoring, echocardiogram, cardiac magnetic resonance, treatment response, and the present relatives of <jats:italic>LMNA<\/jats:italic> carriers. In addition, whole-exome data from 49,960 UK Biobank (UKB) participants were analyzed to describe the overall penetrance of rare <jats:italic>LMNA<\/jats:italic> missense and loss of function (LOF) variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three missense variants in <jats:italic>LMNA<\/jats:italic> were identified in probands with AF as their first and unique clinical manifestation. Other five first-degree relatives, after the screening, also presented <jats:italic>LMNA<\/jats:italic> gene variants. Among 49,960 analyzed UKB participants, 331 carried rare <jats:italic>LMNA<\/jats:italic> missense or LOF variant. Participants who carried a rare <jats:italic>LMNA<\/jats:italic> variant were significantly associated with higher odds of arrhythmic events and of an abnormal ECG in the per-protocol ECG exam (<jats:italic>p<\/jats:italic> = 0.03 and <jats:italic>p<\/jats:italic> = 0.05, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although a rare occurrence, our findings emphasize the possibility of an initial presentation of apparently \u201clone AF\u201d in <jats:italic>LMNA<\/jats:italic> gene variant carriers.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.823717","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T04:52:45Z","timestamp":1649134365000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Effect of Occurrence of Lamin A\/C (LMNA) Genetic Variants in a Cohort of 101 Consecutive Apparent \u201cLone AF\u201d Patients: Results and 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