{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T21:57:19Z","timestamp":1776463039058,"version":"3.51.2"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Cardiology, Warsaw, Poland","award":["2.28\/VII\/23"],"award-info":[{"award-number":["2.28\/VII\/23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background:\u00a0LMNA-related dilated cardiomyopathy (LMNA-DCM) caused by mutations in the lamin A\/C gene (LMNA) is one of the most common forms of hereditary DCM. Due to the high risk of mutation transmission to offspring and the high incidence of ventricular arrhythmia and sudden death even before the onset of heart failure symptoms, it is very important to identify LMNA-mutation carriers. However, many relatives of LMNA-DCM patients do not report to specialized centers for clinical or genetic screening. Therefore, an easily available tool to identify at-risk subjects is needed. Methods: We compared two cohorts of young, asymptomatic relatives of DCM patients who reported for screening: 29 LMNA mutation carriers and 43 individuals from the control group. Receiver operating characteristic (ROC) curves for potential indicators of mutation carriership status were analyzed. Results: PR interval, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (hscTnT) serum levels were higher in the LMNA mutation carrier cohort. Neither group differed significantly with regard to creatinine concentration or left ventricular ejection fraction. The best mutation carriership discriminator was hscTnT level with an optimal cut-off value at 5.5 ng\/L, for which sensitivity and specificity were 86% and 93%, respectively. The median hscTnT level was 11.0 ng\/L in LMNA mutation carriers vs. &lt;3.0 ng\/L in the control group, p &lt; 0.001. Conclusions: Wherever access to genetic testing is limited, LMNA mutation carriership status can be assessed reliably using the hscTnT assay. Among young symptomless relatives of LMNA-DCM patients, a hscTnT level &gt;5.5 ng\/L strongly suggests mutation carriers.<\/jats:p>","DOI":"10.3390\/jcm13113164","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T07:38:39Z","timestamp":1716881919000},"page":"3164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Troponin T Assessment Allows for Identification of Mutation Carriers among Young Relatives of Patients with LMNA-Related Dilated Cardiomyopathy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6655-0070","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Chmielewski","sequence":"first","affiliation":[{"name":"Unit for Screening Studies in Inherited Cardiovascular Diseases, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8040-5109","authenticated-orcid":false,"given":"Ilona","family":"Kowalik","sequence":"additional","affiliation":[{"name":"Clinical Research Support Centre, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-5145","authenticated-orcid":false,"given":"Gra\u017cyna","family":"Truszkowska","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1834-3848","authenticated-orcid":false,"given":"Ewa","family":"Michalak","sequence":"additional","affiliation":[{"name":"Unit for Screening Studies in Inherited Cardiovascular Diseases, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0890-611X","authenticated-orcid":false,"given":"Joanna","family":"Poni\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Sadowska","sequence":"additional","affiliation":[{"name":"Unit for Screening Studies in Inherited Cardiovascular Diseases, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Kalin","sequence":"additional","affiliation":[{"name":"1st Department of Arrhythmia, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Jaworski","sequence":"additional","affiliation":[{"name":"Department of Coronary Artery Disease and Cardiac Rehabilitation, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3106-5427","authenticated-orcid":false,"given":"Ilona","family":"Minota","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7200-6178","authenticated-orcid":false,"given":"Jolanta","family":"Krzyszto\u0144-Russjan","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9277-0552","authenticated-orcid":false,"given":"Tomasz","family":"Zieli\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Heart Failure and Transplantology, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-5526","authenticated-orcid":false,"given":"Rafa\u0142","family":"P\u0142oski","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1451-2069","authenticated-orcid":false,"given":"Zofia Teresa","family":"Bili\u0144ska","sequence":"additional","affiliation":[{"name":"Unit for Screening Studies in Inherited Cardiovascular Diseases, National Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1093\/eurheartj\/ehm342","article-title":"Classification of the cardiomyopathies: A position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"29","author":"Elliott","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1093\/eurheartj\/ehad194","article-title":"2023 ESC Guidelines for the management of cardiomyopathies","volume":"44","author":"Arbelo","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1161\/CIRCRESAHA.121.318157","article-title":"The Complex and Diverse Genetic Architecture of Dilated Cardiomyopathy","volume":"128","author":"Hershberger","year":"2021","journal-title":"Circ. Res."},{"key":"ref_4","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_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","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/j.jacc.2016.08.058","article-title":"Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A\/C Mutation Carriers","volume":"68","author":"Kumar","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mariani, M.V., Pierucci, N., Fanisio, F., Laviola, D., Silvetti, G., Piro, A., La Fazia, V.M., Chimenti, C., Rebecchi, M., and Drago, F. (2024). Inherited Arrhythmias in the Pediatric Population: An Updated Overview. Medicina, 60.","DOI":"10.3390\/medicina60010094"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e012937","DOI":"10.1161\/JAHA.119.012937","article-title":"Exercise is Associated With Impaired Left Ventricular Systolic Function in Patients with Lamin A\/C Genotype","volume":"9","author":"Hasselberg","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","unstructured":"Chmielewski, P., Michalak, E., Kowalik, I., Franaszczyk, M., Sobieszczanska-Malek, M., Truszkowska, G., Stepien-Wojno, M., Biernacka, E.K., Foss-Nieradko, B., and Lewandowski, M. (2020). Can Circulating Cardiac Biomarkers Be Helpful in the Assessment of LMNA Mutation Carriers?. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051443"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.cca.2010.12.034","article-title":"Multicenter analytical evaluation of a high-sensitivity troponin T assay","volume":"412","author":"Saenger","year":"2011","journal-title":"Clin. Chim. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chmielewski, P., Truszkowska, G., Kowalik, I., Rydzanicz, M., Michalak, E., Sobieszcza\u0144ska-Ma\u0142ek, M., Franaszczyk, M., Stawi\u0144ski, P., St\u0119pie\u0144-Wojno, M., and Or\u0119ziak, A. (2021). Titin-Related Dilated Cardiomyopathy: The Clinical Trajectory and the Role of Circulating Biomarkers in the Clinical Assessment. Diagnostics, 12.","DOI":"10.21203\/rs.3.rs-692235\/v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1016\/j.jacc.2012.08.969","article-title":"ACCF 2012 expert consensus document on practical clinical considerations in the interpretation of troponin elevations: A report of the American College of Cardiology Foundation task force on Clinical Expert Consensus Documents","volume":"60","author":"Newby","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1136\/heartjnl-2012-303202","article-title":"Analytically false or true positive elevations of high sensitivity cardiac troponin: A systematic approach","volume":"100","author":"Vafaie","year":"2014","journal-title":"Heart"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1080\/10408363.2017.1285268","article-title":"High-sensitivity cardiac troponin assays: From improved analytical performance to enhanced risk stratification","volume":"54","author":"Kozinski","year":"2017","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jacc.2010.03.037","article-title":"Exercise-induced cardiac troponin elevation: Evidence, mechanisms, and implications","volume":"56","author":"Shave","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"80","DOI":"10.14740\/jocmr4664","article-title":"False-Positive Causes in Serum Cardiac Troponin Levels","volume":"14","author":"Chaulin","year":"2022","journal-title":"J. Clin. Med. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s12964-024-01546-5","article-title":"From gene to mechanics: A comprehensive insight into the mechanobiology of LMNA mutations in cardiomyopathy","volume":"22","author":"Veltrop","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/01.hco.0000221575.33501.58","article-title":"Lamin A\/C and cardiac diseases","volume":"21","author":"Sylvius","year":"2006","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1136\/jmg.2004.023283","article-title":"In vivo and in vitro examination of the functional significances of novel lamin gene mutations in heart failure patients","volume":"42","author":"Sylvius","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S0022-510X(98)00130-0","article-title":"Ultrastructural abnormality of sarcolemmal nuclei in Emery-Dreifuss muscular dystrophy (EDMD)","volume":"159","author":"Fidzianska","year":"1998","journal-title":"J. Neurol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/jhg.2010.137","article-title":"A new c.1621 C > G, p.R541G lamin A\/C mutation in a family with DCM and regional wall motion abnormalities (akinesis\/dyskinesis): Genotype-phenotype correlation","volume":"56","author":"Labib","year":"2011","journal-title":"J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Saj, M., Bilinska, Z.T., Tarnowska, A., Sioma, A., Bolongo, P., Sobieszczanska-Malek, M., Michalak, E., Golen, D., Mazurkiewicz, L., and Malek, L. (2013). LMNA mutations in Polish patients with dilated cardiomyopathy: Prevalence, clinical characteristics, and in vitro studies. BMC Med. Genet., 14.","DOI":"10.1186\/1471-2350-14-55"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e000474","DOI":"10.1136\/openhrt-2016-000474","article-title":"Clinical disease presentation and ECG characteristics of LMNA mutation carriers","volume":"4","author":"Ollila","year":"2017","journal-title":"Open Heart"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/BF03256434","article-title":"Variants of the lamin A\/C (LMNA) gene in non-valvular atrial fibrillation patients: A possible pathogenic role of the Thr528Met mutation","volume":"16","author":"Saj","year":"2012","journal-title":"Mol. Diagn. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/ejhf.3168","article-title":"Role of arrhythmic phenotype in prognostic stratification and management of dilated cardiomyopathy","volume":"26","author":"Setti","year":"2024","journal-title":"Eur. J. Heart Fail."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"823717","DOI":"10.3389\/fcvm.2022.823717","article-title":"Effect of Occurrence of Lamin A\/C (LMNA) Genetic Variants in a Cohort of 101 Consecutive Apparent \u201cLone AF\u201d Patients: Results and Insights","volume":"9","author":"Pessente","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/j.jacc.2021.08.039","article-title":"Association of Genetic Variants With Outcomes in Patients with Nonischemic Dilated Cardiomyopathy","volume":"78","author":"Ochoa","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.jacc.2019.06.072","article-title":"Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy","volume":"74","author":"Gigli","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4050","DOI":"10.1093\/eurheartj\/ehaa083","article-title":"High-sensitivity cardiac troponin assays for cardiovascular risk stratification in the general population","volume":"41","author":"Farmakis","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Stege, N.M., de Boer, R.A., van den Berg, M.P., and Sillj\u00e9, H.H.W. (2021). The Time Has Come to Explore Plasma Biomarkers in Genetic Cardiomyopathies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062955"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/11\/3164\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:49:34Z","timestamp":1760107774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/11\/3164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,28]]},"references-count":34,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["jcm13113164"],"URL":"https:\/\/doi.org\/10.3390\/jcm13113164","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,28]]}}}