{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:07:27Z","timestamp":1790698047693,"version":"4.1.0"},"reference-count":17,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"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>Dilated cardiomyopathy (DCM) has significant morbidity and mortality. Familial transmission is reported in 20\u201335% of cases, highlighting the role of genetics in this disorder. We present an interesting family in which the index case is a 64-year-old woman who survived a sudden cardiac arrest. She presented left ventricular dilatation and dysfunction, which indicated the presence of DCM, as well as a history of DCM and sudden arrest in her family (mother and sister). Genetic testing identified a heterozygous mutation c.74A &gt; G missense change that causes an amino acid, p.Glu25Gly, change in the N-terminal domain of the SCN5A protein. After performing an exhaustive family medical history, we found that this previously not described mutation segregated within the family. All relatives with the DCM phenotype were carriers, whereas none of the noncarriers showed signs of heart disease, so this mutation is the most likely cause of the disease. This is the first time that a variant in the N-terminal domain of SCN5A has been associated with DCM.<\/jats:p>","DOI":"10.3390\/genes12121889","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T05:23:02Z","timestamp":1638163382000},"page":"1889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Familial Dilated Cardiomyopathy and Sudden Cardiac Arrest: New Association with a SCN5A Mutation"],"prefix":"10.3390","volume":"12","author":[{"given":"Yolanda","family":"Rico","sequence":"first","affiliation":[{"name":"Cardiology Department, Hospital Universitari Son Espases, 07120 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francisca","family":"Ramis","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitari Son Espases, 07120 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montse","family":"Massot","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Toulouse, H\u00f4pital de Rangueil, 31400 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8739-6081","authenticated-orcid":false,"given":"Laura","family":"Torres-Juan","sequence":"additional","affiliation":[{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain"},{"name":"Unit of Molecular Diagnostics and Clinical Genetics, Hospital Universitari Son Espases, 07120 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Pons","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitari Son Espases, 07120 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Fortuny","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitari Son Espases, 07120 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9222-325X","authenticated-orcid":false,"given":"Tomas","family":"Ripoll-Vera","sequence":"additional","affiliation":[{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain"},{"name":"Cardiology Department, Hospital Universitari Son Llatzer, 07198 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitari Son Espases, 07120 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Peral","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitari Son Espases, 07120 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Rossello","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitari Son Espases, 07120 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9374-1219","authenticated-orcid":false,"given":"Dami\u00e0","family":"Heine Su\u00f1er","sequence":"additional","affiliation":[{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain"},{"name":"Unit of Molecular Diagnostics and Clinical Genetics, Hospital Universitari Son Espases, 07120 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/S0140-6736(16)31713-5","article-title":"Dilated cardiomyopathy","volume":"390","author":"Weintraub","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gaertner, A., Bloebaum, J., Brodehl, A., Klauke, B., Sielemann, K., Kassner, A., Fox, H., Morshuis, M., Tiesmeier, J., and Schulz, U. (2021). The Combined Human Genotype of Truncating TTN and RBM20 Mutations Is Associated with Severe and Early Onset of Dilated Cardiomyopathy. Genes, 12.","DOI":"10.3390\/genes12060883"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Alimadadi, A., Munroe, P.B., Joe, B., and Cheng, X. (2020). Meta-analysis of dilated cardiomyopathy using cardiac RNA-Seq transcriptomic datasets. Genes, 11.","DOI":"10.3390\/genes11010060"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"My, I., and Di Pasquale, E. (2021). Genetic Cardiomyopathies: The Lesson Learned from hiPSCs. J. Clin. Med., 10.","DOI":"10.3390\/jcm10051149"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcvm.2018.00139","article-title":"A New Cardiac Channelopathy: From Clinical Phenotypes to Molecular Mechanisms Associated with Nav1.5 Gating Pores","volume":"5","author":"Moreau","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/j.hrthm.2014.05.031","article-title":"SCN5A-related dilated cardiomyopathy: What do we know?","volume":"11","author":"Amin","year":"2014","journal-title":"Heart Rhythm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1161\/01.CIR.0000144458.58660.BB","article-title":"SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia","volume":"110","author":"McNair","year":"2004","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1016\/j.jacc.2010.09.084","article-title":"SCN5A mutations associate with arrhythmic dilated cardiomyopathy and commonly localize to the voltage-sensing mechanism","volume":"57","author":"McNair","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1093\/cvr\/cvw234","article-title":"Multilevel analyses of SCN5A mutations in arrhythmogenic right ventricular dysplasia\/cardiomyopathy suggest non-canonical mechanisms for disease pathogenesis","volume":"113","author":"TeRiele","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1016\/j.bbamcr.2016.02.014","article-title":"The role of mutations in the SCN5A gene in cardiomyopathies","volume":"1863","author":"Zaklyazminskaya","year":"2016","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.jacep.2018.03.006","article-title":"Clinical Spectrum of SCN5A Mutations: Long QT Syndrome, Brugada Syndrome, and Cardiomyopathy","volume":"4","author":"Wilde","year":"2018","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Asatryan, B. (2019). Cardiac Sodium Channel Dysfunction and Dilated Cardiomyopathy: A Contemporary Reappraisal ofPathophysiological Concepts. J. Clin. Med., 8.","DOI":"10.3390\/jcm8071029"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.echo.2014.10.003","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"28","author":"Lang","year":"2015","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: The Human Genomic Variant Search Engine","volume":"35","author":"Kopanos","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/cvr\/cvs211","article-title":"Dominant-negative effect of SCN5A N-terminal mutations through the interaction of Na(v)1.5 \u03b1-subunits","volume":"96","author":"Clatot","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1080\/19336950.2020.1805999","article-title":"Calmodulin binds to the N-terminal domain of the cardiac sodium channel Nav1.5","volume":"14","author":"Wang","year":"2020","journal-title":"Channels"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/12\/1889\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:35:54Z","timestamp":1760168154000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/12\/1889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,25]]},"references-count":17,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["genes12121889"],"URL":"https:\/\/doi.org\/10.3390\/genes12121889","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,25]]}}}