{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T05:40:07Z","timestamp":1752471607722,"version":"3.41.2"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"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. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital heart defects (CHDs) represent the leading cause of neonatal mortality among congenital abnormalities. Genetic factors, such as <jats:italic>EVC<\/jats:italic>2 gene mutations and other genetic alterations, constitute a major cause of CHD. Thus, determining the genetic etiology of fetal CHDs is crucial for optimizing pregnancy management and informing future reproductive decisions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>Here, we describe a male fetus with complex CHD who was diagnosed at 25\u2005weeks of gestation, delivered at full term, and died prematurely within a month due to heart failure. The cardiac abnormalities observed included an atrial septal defect developing from a patent foramen ovale, mitral valve regurgitation, dilated right ventricle and left atrium, aortic stenosis, and aortic arch dysplasia. Novel compound heterozygosity of the <jats:italic>EVC<\/jats:italic>2 gene, including a non-sense mutation (p.W828Ter) and two cis missense mutations (p.E87G and p.S217C), was identified by prenatal trio-whole-exome sequencing of amniotic fluid, followed by validation using Sanger sequencing. This novel <jats:italic>EVC<\/jats:italic>2 genotype was supposed to potentially affect fetal cardiac development, given the variable clinical heterogeneity of the <jats:italic>EVC<\/jats:italic>2 mutation-associated phenotype. This case represents the first identification of the <jats:italic>EVC<\/jats:italic>2 p.E87G and p.S217C, and the isolated CHD without visible skeletal dysplasia is an important feature of our case.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study expands the genotypic and phenotypic spectra of <jats:italic>the EVC<\/jats:italic>2 gene. We recommend including the <jats:italic>EVC<\/jats:italic>2 gene in preconception carrier screening and prenatal diagnosis for CHDs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2025.1352571","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T05:25:42Z","timestamp":1752470742000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: A novel compound heterozygosity of the EVC2 gene identified in a Chinese pedigree with congenital heart defect"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiayuan","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengcheng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keqin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangshuang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/S2352-4642(19)30402-X","article-title":"Global, regional, and national burden of congenital heart disease, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"4","year":"2020","journal-title":"Lancet Child Adolesc Health"},{"key":"B2","doi-asserted-by":"publisher","first-page":"879","DOI":"10.3390\/biom9120879","article-title":"Genetics of congenital heart disease","volume":"9","author":"Williams","year":"2019","journal-title":"Biomolecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1161\/CIRCRESAHA.116.309140","article-title":"Genetics and genomics of congenital heart disease","volume":"120","author":"Zaidi","year":"2017","journal-title":"Circ Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/S1096-7192(02)00178-6","article-title":"A new gene, EVC2, is mutated in Ellis-van Creveld syndrome","volume":"77","author":"Galdzicka","year":"2002","journal-title":"Mol Genet Metab"},{"key":"B5","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1086\/368063","article-title":"Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome","volume":"72","author":"Ruiz-Perez","year":"2003","journal-title":"Am J Hum Genet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/73508","article-title":"Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis","volume":"24","author":"Ruiz-Perez","year":"2000","journal-title":"Nat Genet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/1750-1172-2-27","article-title":"Ellis-van Creveld syndrome","volume":"2","author":"Baujat","year":"2007","journal-title":"Orphanet J Rare Dis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1111\/cga.12155","article-title":"Truncation and microdeletion of EVC\/EVC2 with missense mutation of EFCAB7 in Ellis-van Creveld syndrome","volume":"56","author":"Nguyen","year":"2016","journal-title":"Congenit Anom (Kyoto)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1007\/s00246-011-0006-9","article-title":"Ellis-van Creveld syndrome and congenital heart defects: presentation of an additional 32 cases","volume":"32","author":"Hills","year":"2011","journal-title":"Pediatr Cardiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.gene.2012.02.030","article-title":"Ellis-van Creveld syndrome in a fetus with rhizomelia and polydactyly. 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