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Genetic screening of families with severe cardiomyopathies underlines the role of genetic variations in cardiac\u2010specific genes. The present study details the clinical and genetic characterization of a malignant dilated cardiomyopathy (DCM) case in a 1\u2010year\u2010old Mexican child who presented a severe left ventricular dilation and dysfunction that led to SCD. A total of 132 genes (48 structure\u2010 and 84 electrical\u2010related genes) were examined by next generation sequencing to identify potential causative mutations in comparison to control population. <jats:italic>In silico<\/jats:italic> analysis identified only two deleterious heterozygous mutations within an evolutionarily well\u2010conserved region of the sarcomeric genes <jats:italic>ACTC1<\/jats:italic>\/cardiac actin (c.664G\u2009&gt;\u2009A\/p.Ala222Thr) and <jats:italic>TTN<\/jats:italic>\/titin (c.33250G\u2009&gt;\u2009A\/p.Glu11084Lys). Further pedigree analysis revealed the father of the index case to carry with the <jats:italic>TTN<\/jats:italic> mutation. Surprisingly, the <jats:italic>ACTC1<\/jats:italic> mutation was not harbored by any first\u2010degree family member. Computational 3D modeling of the mutated proteins showed electrostatic and conformational shifts of cardiac actin compared to wild\u2010type version, as well as changes in the stability of the compact\/folded states of titin that normally contributes to avoid mechanic damage. In conclusion, our findings suggest a likely pathogenic <jats:italic>de novo<\/jats:italic> mutation in <jats:italic>ACTC1<\/jats:italic> in coexpression of a <jats:italic>TTN<\/jats:italic> variant as possible causes of an early onset of a severe DCM and premature death. These results may increase the known clinical pathogenic variations that may critically alter the structure of the heart, whose fatality could be prevented when rapidly detected.<\/jats:p>","DOI":"10.1155\/crig\/9517735","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T11:11:34Z","timestamp":1735384294000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>A De Novo<\/i> Mutation in <i>ACTC1<\/i> and a <i>TTN<\/i> Variant Linked to a Severe Sporadic Infant Dilated Cardiomyopathy Case"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0230-7346","authenticated-orcid":false,"given":"Jose G.","family":"Acu\u00f1a-Ochoa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-1992","authenticated-orcid":false,"given":"Norma A.","family":"Balderr\u00e1bano-Saucedo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2563-6171","authenticated-orcid":false,"given":"Ana C.","family":"Cepeda-Nieto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0169-6129","authenticated-orcid":false,"given":"Maria Y.","family":"Alvarado-Cervantes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5423-7351","authenticated-orcid":false,"given":"Vianca L.","family":"Ibarra-Garcia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4660-5649","authenticated-orcid":false,"given":"Daniel","family":"Barr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"Gage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4139-4881","authenticated-orcid":false,"given":"Ryan","family":"Pfeiffer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0994-8434","authenticated-orcid":false,"given":"Dan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-3807","authenticated-orcid":false,"given":"Hector","family":"Barajas-Martinez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,28]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2018.08.026"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-84882-927-5_1"},{"key":"e_1_2_12_3_2","volume-title":"What is Cardiomyopathy? 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