{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T22:38:24Z","timestamp":1778020704452,"version":"3.51.4"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize the cardiac phenotype associated with the novel pathogenic variant (c.1526del) of <jats:italic>LMNA<\/jats:italic> gene, which we identified in a large, six-generation family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>A family tree was constructed. The clinical data of living and deceased family members were collected. DNA samples from 7 family members were analyzed for <jats:italic>LMNA<\/jats:italic> mutations using whole-exome high-throughput sequencing technology. The clinical presentation of pathogenic variant carriers was evaluated. In this six-generation family (<jats:italic>n<\/jats:italic>\u2009=\u200967), one member experienced sudden death at the age of 40-years-old. Three pathogenic variant carriers were identified to possess a novel heterozygous deletion mutation in <jats:italic>LMNA<\/jats:italic> gene (HGVS: NM_170707.4, c.1526del) located at exon 9 of <jats:italic>LMNA<\/jats:italic> chr1:156137145, which creates a premature translational stop signal (p.Pro509Leufs*39) in the LMNA gene and results in an mutant lamin A protein product. The main symptoms of the pathogenic variant carriers were palpitation, fatigue, and syncope, which typically occurred around 20-years-old. AV-conduction block and non-sustained ventricular tachycardia were the first signs of disease and would rapidly progress to atrial standstill around 30-years-old. Significant right atrial enlargement and bicuspid aortic valve malformation was also commonly seen in patients who carried this pathogenic variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The pathogenic variant of c.1526del p.P509Lfs*39 was a frameshift deletion located at exon 9 of <jats:italic>LMNA<\/jats:italic> chr1:156137145 and causes severe right atrial enlargement, sick sinus syndrome, atrial standstill, ventricular tachycardia, and bicuspid aortic valve malformation. Our findings expand the phenotypic spectrum of novel <jats:italic>LMNA<\/jats:italic> gene mutations.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2023.1109008","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T06:31:31Z","timestamp":1688365891000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel pathogenic variant in LMNA gene identified in a six-generation family causing atrial cardiomyopathy and associated right atrial conduction 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