{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T16:27:14Z","timestamp":1761841634397,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dilated cardiomyopathy (DCM) is a major cause of nonischemic heart failure and death in young adults. Next generation sequencing (NGS) has become part of the diagnostic workup in idiopathic and familial DCM. More than 50 DCM genes have been identified, revealing great molecular heterogeneity and variable diagnostic yield. Interpretation of variant pathogenicity is challenging particularly in underrepresented populations, as pathogenic variant databases include studies mainly from European\/Caucasian populations. To date, no studies on genomic diagnosis of DCM have been conducted in Mexico.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited 55 unrelated DCM patients, 22 familial (F\u2010DCM), and 33 idiopathic (I\u2010DCM), and performed site\u2010directed NGS seeking causal mutations. Diagnostic yield was defined as the proportion of individuals with at least one pathogenic (P) or likely pathogenic (LP) variant in DCM genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall diagnostic yield was 47.3%, and higher in F\u2010DCM (63.6%) than in I\u2010DCM (36.4%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.047). Overall, NGS disclosed 41 variants of clinical interest (61.0% novel), 27 were classified as P\/LP and 14 of unknown clinical significance. Of P\/LP variants, 10 were A\u2010band region <jats:italic>TTN<\/jats:italic> truncating variants, five were found in <jats:italic>DSP<\/jats:italic> (18.5%), five in <jats:italic>MYH7<\/jats:italic> (18.5%), two in <jats:italic>LMNA<\/jats:italic> (7.4%), and one in <jats:italic>RBM20<\/jats:italic>, <jats:italic>ABCC9<\/jats:italic>, <jats:italic>FKTN<\/jats:italic>, <jats:italic>ACTA1<\/jats:italic>, and <jats:italic>TNNT2<\/jats:italic>. NGS findings suggested autosomal recessive inheritance in three families, two with <jats:italic>DSP<\/jats:italic> loss of function mutations in affected individuals. The increasing number of mutation reports in DCM, increasing knowledge on the functional consequences of mutations, mutational hotspots and functional domains of DCM\u2010related proteins, the recent refinement ACMG\/ClinGen Guidelines, and co\u2010segregation analysis in DCM families helped increase the diagnostic yield.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first NGS study performed in a group of Mexican DCM patients, contributing to understand the mutational spectrum and complexity of DCM molecular diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1504","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T11:55:07Z","timestamp":1600948507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genomic study of dilated cardiomyopathy in a group of Mexican patients using site\u2010directed next generation sequencing"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4511-4557","authenticated-orcid":false,"given":"Alessandra","family":"Carnevale","sequence":"first","affiliation":[{"name":"Instituto Nacional de Medicina Gen\u00f3mica  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-6658","authenticated-orcid":false,"given":"Sandra","family":"Rosas\u2010Madrigal","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Medicina Gen\u00f3mica  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rigoberto","family":"Rosendo\u2010Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Medicina Gen\u00f3mica  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"L\u00f3pez\u2010Mora","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3077-7825","authenticated-orcid":false,"given":"Sandra","family":"Romero\u2010Hidalgo","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Medicina Gen\u00f3mica  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nydia","family":"Avila\u2010Vazzini","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5129-8108","authenticated-orcid":false,"given":"Leonor","family":"Jacobo\u2010Albavera","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Medicina Gen\u00f3mica  Mexico City 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