{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:45:40Z","timestamp":1766040340730,"version":"3.48.0"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"\n Introduction<\/jats:title>\n \n Bi-allelic pathogenic variants in\n MYBPC3<\/jats:italic>\n cause a rare and lethal neonatal form of hypertrophic cardiomyopathy (HCM) that often evades detection during routine prenatal screening. We report a comprehensive investigation of such a case to highlight the clinical utility of postmortem molecular diagnosis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A two-month-old infant died from sudden-onset acute heart failure. We performed a full forensic autopsy with detailed histological examination and conducted trio-based whole-exome sequencing (WES) on the proband and parents to identify the genetic etiology.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Postmortem examination revealed severe HCM, an atrial septal defect (ASD), and extensive myocardial necrosis and fibrosis. WES identified compound heterozygous pathogenic variants in\n MYBPC3<\/jats:italic>\n : a known paternal splice-site variant (c.2905+1G&gt;A) and a novel maternal truncating frameshift variant (c.836del; p.Gly279Valfs*21). Both variants are predicted to result in a complete loss of protein function.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n This \u201cmolecular autopsy\u201d established a definitive cause for the infant's death, linking a novel variant to a severe pathological phenotype. Crucially, the diagnosis guided the clinical management of the asymptomatic carrier parents, prompting long-term cardiac surveillance and enabling preimplantation genetic testing (PGT) for future family planning. This case demonstrates how integrating molecular diagnostics with forensic pathology facilitates a systems medicine approach, transforming a fatal index case into actionable preventive care for the entire family.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcvm.2025.1726463","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:41:38Z","timestamp":1766040098000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Lethal neonatal hypertrophic cardiomyopathy from compound heterozygous MYBPC3 variants"],"prefix":"10.3389","volume":"12","author":[{"given":"Jianying","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingye","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengrong","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuefeng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xutao","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1136\/jmedgenet-2021-107774","article-title":"Cardiac myosin binding protein-C variants in paediatric-onset hypertrophic cardiomyopathy: natural history and clinical outcomes","volume":"59","author":"Field","year":"2022","journal-title":"J Med Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"10510","DOI":"10.3390\/ijms241310510","article-title":"An update on Mybpc3 gene mutation in hypertrophic cardiomyopathy","volume":"24","author":"Tudurachi","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1161\/CIRCGEN.123.004118","article-title":"Childhood hypertrophic cardiomyopathy caused by Beta-myosin heavy chain variants is associated with a more obstructive but less arrhythmogenic phenotype than myosin-binding protein C disease","volume":"16","author":"Norrish","year":"2023","journal-title":"Circ Genom Precis Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1038\/ejhg.2014.211","article-title":"Compound heterozygous or homozygous truncating Mybpc3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects","volume":"23","author":"Wessels","year":"2015","journal-title":"Eur J Hum Genet"},{"key":"B5","doi-asserted-by":"publisher","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":"B6","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1002\/uog.24881","article-title":"From dotted lines to fetal cardiology: the pioneering contribution of Xin-Fang Wang (1934\u20132021)","volume":"59","author":"Deng","year":"2022","journal-title":"Ultrasound Obstet Gynecol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1206138","DOI":"10.3389\/fcvm.2023.1206138","article-title":"Advanced imaging of fetal cardiac function","volume":"10","author":"Kuhle","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/j.echo.2024.08.012","article-title":"Fetal echocardiography from 10 to 15 weeks of gestation-reliability, genetic associations, and outcomes","volume":"37","author":"Rittey","year":"2024","journal-title":"J Am Soc Echocardiogr"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2929","DOI":"10.2174\/138161210793176428","article-title":"Diagnosis and prognosis of fetal cardiomyopathies: a review","volume":"16","author":"Mongiovi","year":"2010","journal-title":"Curr Pharm Des"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1161\/01.cir.0000437597.44550.5d","article-title":"Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association","volume":"129","author":"Donofrio","year":"2014","journal-title":"Circulation"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1726463\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:41:54Z","timestamp":1766040114000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1726463\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":10,"alternative-id":["10.3389\/fcvm.2025.1726463"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2025.1726463","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"article-number":"1726463"}}