{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:55:28Z","timestamp":1792252528971,"version":"4.4.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"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. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The genetic factors underlying congenital heart disease and heterotaxy (CHD\/HTX) are complex, including copy number variants, loss-of-function mutations, and missense variants, many of which can be detected by high-throughput sequencing. The screening for chromosomal structural variations (SVs) is another important strategy to understand the genetic etiology of CHD\/HTX.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed optical genome mapping (OGM), an innovative technique capable of capturing SVs often missed by traditional cytogenetic methods, to screen for SVs in 12 patients with complex CHD\/HTX. Several patients had previously undergone chromosomal microarray analysis (CMA) or whole exome sequencing (WES), but their genetic diagnoses remained inconclusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      By integrating data from CMA or WES, we analyzed potentially pathogenic SVs in patients with CHD\/HTX. In total, we identified 825 high-confidence SVs, including 609 SVs (73.7%) located in intergenic regions or containing introns, pseudogenes, or RNA genes, while 217 (26.3%) overlapped the coding regions of genes. Analyzed through AnnotSV, DECIPHER and OMIM databases, 7 SVs of interest were identified, including: one previously reported pathogenic SV, three SVs overlapping established CHD\/HTX associated genes (\n                      <jats:italic>NOTCH2<\/jats:italic>\n                      ,\n                      <jats:italic>KDM6A<\/jats:italic>\n                      and\n                      <jats:italic>CBL<\/jats:italic>\n                      ), and three SVs located in\n                      <jats:italic>SMARCA2<\/jats:italic>\n                      and\n                      <jats:italic>CEP164<\/jats:italic>\n                      , which are proposed as candidate susceptibility genes pending further validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings highlight the utility of OGM in analyzing the genetic etiology of CHD\/HTX and contribute to broadening of the complex genetic landscape underlying these diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2025.1673539","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T09:10:52Z","timestamp":1764925852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Optical genome mapping uncovers clinically relevant structural variants in congenital heart disease with heterotaxy"],"prefix":"10.3389","volume":"16","author":[{"given":"Shaojie","family":"Min","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weicheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quannan","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuquan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuolin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1136\/jmedgenet-2021-107775","article-title":"Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects","volume":"59","author":"Bolkier","year":"2022","journal-title":"J. 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