{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:57:37Z","timestamp":1788897457202,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007354","name":"Fondation Lefoulon Delalande","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007354","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle, systolic dysfunction, and normal or reduced thickness of the left ventricular wall. It is a leading cause of heart failure and cardiac death at a young age. Cases with neonatal onset DCM were correlated with severe clinical presentation and poor prognosis. A monogenic molecular etiology accounts for nearly half of cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Family description<\/jats:title><jats:p>Here, we report a family with three deceased offspring at the age of 1\u2009year old. The autopsy of the first deceased infant revealed a DCM. The second infant presented a DCM phenotype with a severely reduced Left Ventricular Ejection Fraction (LVEF) of 10%. Similarly, the third infant showed a severe DCM phenotype with LVEF of 30% as well, in addition to eccentric mitral insufficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exome sequencing was performed for the trio (the second deceased infant and her parents). Data analysis following the autosomal dominant and recessive patterns of inheritance was carried out along with a mitochondrial pathways\u2010based analysis. We identified a homozygous frameshift variant in the <jats:italic>TNNI3<\/jats:italic> gene (c.204delG; p.(Arg69AlafsTer8)). This variant has been recently reported in the ClinVar database in association with cardiac phenotypes as pathogenic or likely pathogenic and classified as pathogenic according to ACMG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genetic counseling was provided for the family and a prenatal diagnosis of choronic villus was proposed in the absence of pre\u2010implantation genetic diagnosis possibilities. Our study expands the case series of early\u2010onset DCM patients with a protein\u2010truncating variant in the <jats:italic>TNNI3<\/jats:italic> gene by reporting three affected infant siblings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2486","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T10:50:23Z","timestamp":1719312623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Homozygous <i>TNNI3<\/i> frameshift variant in a consanguineous family with lethal infantile dilated cardiomyopathy"],"prefix":"10.1002","volume":"12","author":[{"given":"Lilia","family":"Kraoua","sequence":"first","affiliation":[{"name":"Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital, Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assaad","family":"Louati","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit Bechir Hamza Children's Hospital in Tunis  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarra Ben","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Pediatric \u201cA\u201d Department of the Bechir Hamza Children's Hospital, Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesrine","family":"Abida","sequence":"additional","affiliation":[{"name":"Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital, Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monia","family":"Khemiri","sequence":"additional","affiliation":[{"name":"Pediatric \u201cA\u201d Department of the Bechir Hamza Children's Hospital, Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Menif","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit Bechir Hamza Children's Hospital in Tunis  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ridha","family":"Mrad","sequence":"additional","affiliation":[{"name":"Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital, Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0811-418X","authenticated-orcid":false,"given":"St\u00e9phane","family":"Zaffran","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ INSERM, Marseille Medical Genetics  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hager","family":"Jaouadi","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ INSERM, Marseille Medical Genetics  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax2066"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.120.002969"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105498"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.196055"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.635128"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10235518"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.9.7601340"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02188-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjco.2021.07.017"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62590"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abf3274"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110186"},{"key":"e_1_2_9_14_1","volume-title":"GeneReviews\u00ae","author":"Hershberger R. 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