{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:23:08Z","timestamp":1771478588924,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>We report a family with heterozygous deletion of exons 3\u20136 of the LMNA gene. The main presentation of affected family members was characterized by ventricular and supraventricular arrhythmias, atrioventricular (AV) block and sudden cardiac death (SCD) but also by severe dilative cardiomyopathy (DCM). We report on two siblings, a 36-year-old female and her 40-year-old brother, who suffer from heart failure with mildly reduced ejection fraction, AV conduction delays and premature ventricular complexes. Their 65-year-old mother underwent heart transplantation at the age of 55 due to advanced heart failure. Originally, the LMNA mutation was detected in one of the uncles. This index patient and three of his brothers died of SCD as well as their father and aunt. The two siblings were treated with implanted defibrillators in our specialized tertiary heart failure center. This case report places this specific genetic variant in the context of LMNA-associated familial DCM.<\/jats:p>","DOI":"10.3390\/genes13020169","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T08:20:57Z","timestamp":1642580457000},"page":"169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["LMNA Mutation in a Family with a Strong History of Sudden Cardiac Death"],"prefix":"10.3390","volume":"13","author":[{"given":"Laura","family":"Keil","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center Hamburg, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filip","family":"Berisha","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center Hamburg, 20251 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/Luebeck, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorit","family":"Knappe","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center Hamburg, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Kubisch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Hamburg Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moneef","family":"Shoukier","sequence":"additional","affiliation":[{"name":"Prenatal Medicine Munich, Department of Molecular Genetics, 80639 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-0197","authenticated-orcid":false,"given":"Paulus","family":"Kirchhof","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center Hamburg, 20251 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/Luebeck, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa","family":"Fabritz","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center Hamburg, 20251 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/Luebeck, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yorck","family":"Hellenbroich","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rixa","family":"Woitschach","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Hamburg Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Magnussen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center Hamburg, 20251 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/Luebeck, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S0735-1097(02)02954-6","article-title":"Natural History of Dilated Cardiomyopathy Due to Lamin A\/C Gene Mutations","volume":"41","author":"Taylor","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.ahj.2007.07.038","article-title":"High Yield of LMNA Mutations in Patients with Dilated Cardiomyopathy and\/or Conduction Disease Referred to Cardiogenetics Outpatient Clinics","volume":"154","author":"Hofstra","year":"2007","journal-title":"Am. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1056\/NEJM199912023412302","article-title":"Missense Mutations in the Rod Domain of the Lamin A\/C Gene as Causes of Dilated Cardiomyopathy and Conduction-System Disease","volume":"341","author":"Fatkin","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00109-004-0589-1","article-title":"Meta-Analysis of Clinical Characteristics of 299 Carriers of LMNA Gene Mutations: Do Lamin A\/C Mutations Portend a High Risk of Sudden Death?","volume":"83","author":"Bonne","year":"2005","journal-title":"J. Mol. Med. Berl. Ger."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.jacc.2011.08.078","article-title":"Risk Factors for Malignant Ventricular Arrhythmias in Lamin a\/c Mutation Carriers a European Cohort Study","volume":"59","author":"Arbustini","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","first-page":"563","article-title":"Risk Prediction of Ventricular Arrhythmias and Myocardial Function in Lamin A\/C Mutation Positive Subjects","volume":"16","author":"Hasselberg","year":"2014","journal-title":"EP Eur."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/6799","article-title":"Mutations in the Gene Encoding Lamin A\/C Cause Autosomal Dominant Emery-Dreifuss Muscular Dystrophy","volume":"21","author":"Bonne","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1093\/hmg\/9.9.1453","article-title":"Identification of Mutations in the Gene Encoding Lamins A\/C in Autosomal Dominant Limb Girdle Muscular Dystrophy with Atrioventricular Conduction Disturbances (LGMD1B)","volume":"9","author":"Muchir","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.jacc.2008.07.021","article-title":"Lamin A\/C Gene and the Heart: How Genetics May Impact Clinical Care","volume":"52","author":"Mestroni","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nrm950","article-title":"Lamins: Building Blocks or Regulators of Gene Expression?","volume":"3","author":"Hutchison","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1161\/CIRCRESAHA.118.314177","article-title":"Genomic Reorganization of Lamin-Associated Domains in Cardiac Myocytes Is Associated With Differential Gene Expression and DNA Methylation in Human Dilated Cardiomyopathy","volume":"124","author":"Cheedipudi","year":"2019","journal-title":"Circ. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1093\/cvr\/cvaa116","article-title":"Genetic Basis and Molecular Biology of Cardiac Arrhythmias in Cardiomyopathies","volume":"116","author":"Marian","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1038\/s41467-019-09929-w","article-title":"The K219T-Lamin Mutation Induces Conduction Defects through Epigenetic Inhibition of SCN5A in Human Cardiac Laminopathy","volume":"10","author":"Salvarani","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1161\/CIRCULATIONAHA.118.039410","article-title":"Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies","volume":"140","author":"Wahbi","year":"2019","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.hrthm.2009.01.037","article-title":"A Novel Mutation in LAMIN A\/C Is Associated with Isolated Early-Onset Atrial Fibrillation and Progressive Atrioventricular Block Followed by Cardiomyopathy and Sudden Cardiac Death","volume":"6","author":"Pan","year":"2009","journal-title":"Heart Rhythm"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1002\/ehf2.12822","article-title":"Case Series: LMNA-Related Dilated Cardiomyopathy Presents with Reginal Wall Akinesis and Transmural Late Gadolinium Enhancement","volume":"7","author":"Wang","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11010-013-1734-3","article-title":"A Novel Mutation of the LMNA Gene in a Family with Dilated Cardiomyopathy, Conduction System Disease, and Sudden Cardiac Death of Young Females","volume":"382","author":"Chen","year":"2013","journal-title":"Mol. Cell. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/boc.201400033","article-title":"Role of Nuclear Lamin A\/C in Cardiomyocyte Functions","volume":"106","author":"Carmosino","year":"2014","journal-title":"Biol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.3389\/fphys.2018.01356","article-title":"Role of Lamin A\/C Gene Mutations in the Signaling Defects Leading to Cardiomyopathies","volume":"9","author":"Gerbino","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1161\/CIRCULATIONAHA.111.025528","article-title":"Sudden Death from Genetic and Acquired Cardiomyopathies","volume":"125","author":"McKenna","year":"2012","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/hmg\/ddi017","article-title":"Mouse Model Carrying H222P-Lmna Mutation Develops Muscular Dystrophy and Dilated Cardiomyopathy Similar to Human Striated Muscle Laminopathies","volume":"14","author":"Arimura","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1093\/hmg\/ddw090","article-title":"ERK1\/2 Directly Acts on CTGF\/CCN2 Expression to Mediate Myocardial Fibrosis in Cardiomyopathy Caused by Mutations in the Lamin A\/C Gene","volume":"25","author":"Chatzifrangkeskou","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e000915","DOI":"10.1136\/openhrt-2018-000915","article-title":"Lamin Mutation Location Predicts Cardiac Phenotype Severity: Combined Analysis of the Published Literature","volume":"5","author":"Captur","year":"2018","journal-title":"Open Heart"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/mgg3.187","article-title":"Next Generation Sequencing-Based Copy Number Analysis Reveals Low Prevalence of Deletions and Duplications in 46 Genes Associated with Genetic Cardiomyopathies","volume":"4","author":"Pugh","year":"2016","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00395-010-0085-4","article-title":"Genetic and Ultrastructural Studies in Dilated Cardiomyopathy Patients: A Large Deletion in the Lamin A\/C Gene Is Associated with Cardiomyocyte Nuclear Envelope Disruption","volume":"105","author":"Gupta","year":"2010","journal-title":"Basic Res. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1016\/j.jacc.2007.02.063","article-title":"Severe Myocardial Fibrosis Caused by a Deletion of the 5\u2032 End of the Lamin A\/C Gene","volume":"49","author":"Tio","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_27","first-page":"395","article-title":"Deletion of Entire LMNA Gene as a Cause of Cardiomyopathy","volume":"6","author":"Cirino","year":"2020","journal-title":"Hear. Case Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1399-0004.2005.00447.x","article-title":"LMNA Mutation Position Predicts Organ System Involvement in Laminopathies","volume":"68","author":"Hegele","year":"2005","journal-title":"Clin. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/eurheartj\/ehx596","article-title":"Lamin A\/C Cardiomyopathy: Young Onset, High Penetrance, and Frequent Need for Heart Transplantation","volume":"39","author":"Hasselberg","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.jacc.2008.06.044","article-title":"Long-Term Outcome and Risk Stratification in Dilated Cardiolaminopathies","volume":"52","author":"Pasotti","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/S0735-1097(02)01724-2","article-title":"Autosomal Dominant Dilated Cardiomyopathy with Atrioventricular Block: A Lamin A\/C Defect-Related Disease","volume":"39","author":"Arbustini","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1016\/j.hrthm.2013.06.020","article-title":"Implantable Cardioverter-Defibrillators in Lamin A\/C Mutation Carriers with Cardiac Conduction Disorders","volume":"10","author":"Anselme","year":"2013","journal-title":"Heart Rhythm"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1093\/eurheartj\/ehab364","article-title":"2021 ESC Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy","volume":"42","author":"Glikson","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1093\/eurheartj\/ehv316","article-title":"2015 ESC Guidelines for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)","volume":"36","author":"Priori","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1093\/eurheartj\/ehr451","article-title":"Mutations in the Lamin A\/C Gene Mimic Arrhythmogenic Right Ventricular Cardiomyopathy","volume":"33","author":"Quarta","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Forleo, C., Carmosino, M., Resta, N., Rampazzo, A., Valecce, R., Sorrentino, S., Iacoviello, M., Pisani, F., Procino, G., and Gerbino, A. (2015). Clinical and Functional Characterization of a Novel Mutation in Lamin a\/c Gene in a Multigenerational Family with Arrhythmogenic Cardiac Laminopathy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121723"},{"key":"ref_37","first-page":"30","article-title":"Late Gadolinium Enhanced Cardiovascular Magnetic Resonance of Lamin A\/C Gene Mutation Related Dilated Cardiomyopathy","volume":"13","author":"Jurkko","year":"2011","journal-title":"J. Cardiovasc. Magn. Reson. Off. J. Soc. Cardiovasc. Magn. Reson."},{"key":"ref_38","first-page":"1864","article-title":"Late Gadolinium Enhancement Role in Arrhythmic Risk Stratification of Patients with LMNA Cardiomyopathy: Results from a Long-Term Follow-up Multicentre Study","volume":"22","author":"Peretto","year":"2020","journal-title":"EP Eur."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jchf.2016.09.017","article-title":"Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy: Systematic Review and Meta-Analysis","volume":"5","author":"Anguera","year":"2017","journal-title":"JACC Heart Fail."},{"key":"ref_40","first-page":"326","article-title":"Dilated Cardiomyopathy and Arrhythmogenic Left Ventricular Cardiomyopathy: A Comprehensive Genotype-Imaging Phenotype Study","volume":"21","author":"Augusto","year":"2020","journal-title":"Eur. Heart J. Cardiovasc. 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