{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:18:36Z","timestamp":1777393116210,"version":"3.51.4"},"reference-count":92,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017268","name":"Berlin Institute of Health","doi-asserted-by":"publisher","award":["BIH-CRG2-ConDi"],"award-info":[{"award-number":["BIH-CRG2-ConDi"]}],"id":[{"id":"10.13039\/501100017268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Congenital heart defects (CHDs) are the most common birth defect in human with an incidence of almost 1% of all live births. Most cases have a multifactorial origin with both genetics and the environment playing a role in its development and progression. Adding an epigenetic component to this aspect is exemplified by monozygotic twins which share the same genetic background but have a different disease status. As a result, the interplay between the genetic, epigenetic and the environmental conditions might contribute to the etiology and phenotype. To date, the underlying causes of the majority of CHDs remain poorly understood. In this study, we performed genome-wide high-throughput sequencing to examine the genetic, structural genomic and epigenetic differences of two identical twin pairs discordant for Tetralogy of Fallot (TOF), representing the most common cyanotic form of CHDs. Our results show the almost identical genetic and structural genomic identity of the twins. In contrast, several epigenetic alterations could be observed given by DNA methylation changes in regulatory regions of known cardiac-relevant genes. Overall, this study provides first insights into the impact of genetic and especially epigenetic factors underlying monozygotic twins discordant for CHD like TOF.<\/jats:p>","DOI":"10.3390\/jcdd7040055","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T07:49:54Z","timestamp":1606895394000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Needle in the Haystack\u2014Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot"],"prefix":"10.3390","volume":"7","author":[{"given":"Marcel","family":"Grunert","sequence":"first","affiliation":[{"name":"Cardiovascular Genetics, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), 10178 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Appelt","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), 10178 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Grossfeld","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of California San Diego, Rady\u2019s Hospital MC 5004, San Diego, CA 92123, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7135-3298","authenticated-orcid":false,"given":"Silke R.","family":"Sperling","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), 10178 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany"},{"name":"Department of Biology, Chemistry, and Pharmacy, Freie Universit\u00e4t Berlin, 14195 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1016\/j.jacc.2011.08.025","article-title":"Birth prevalence of congenital heart disease worldwide: A systematic review and meta-analysis","volume":"58","author":"Konings","year":"2011","journal-title":"J. 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