{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T09:30:09Z","timestamp":1776763809992,"version":"3.51.2"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"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:p><jats:bold>Background:<\/jats:bold> Emery\u2013Dreifuss muscular dystrophy (EDMD) is a rare disease characterized by early joint contractures, slowly progressive muscular dystrophy, and cardiac involvement, which includes arrhythmia, dilated cardiomyopathy, hypertrophic cardiomyopathy, heart failure, and sudden death.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Clinical data of the proband and family members were collected. The next-generation sequencing technology was used to analyze the pathogenic variants and copy number variations. Polymerase chain reaction was used to sequence the breakpoints of gene locus rearrangements.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Here, we report two siblings with EDMD in a family. The proband, a 17-year-old boy, manifested a dilated right heart, bradycardia, mild muscle weakness, and joint contractures. His younger brother only showed a mild bowing limitation with elevated creatine kinase. Next-generation sequencing revealed the complete deletion of <jats:italic>EMD<\/jats:italic> and a rearrangement in <jats:italic>FLNA<\/jats:italic> (exon29_48dup) in these two patients. The <jats:italic>EMD<\/jats:italic> deletion and partial <jats:italic>FLNA<\/jats:italic> duplication were accompanied by a 5 bp overlap (GTCCC) on the background of the <jats:italic>FLNA-EMD<\/jats:italic> inversion. These findings support the pathogenic mechanism of microhomology-mediated nonhomologous end joining.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> We report two siblings with complete <jats:italic>EMD<\/jats:italic> deletion and <jats:italic>FLNA<\/jats:italic> duplication in a family. A microhomology-mediated nonhomologous end joining event involving <jats:italic>EMD<\/jats:italic> and <jats:italic>FLNA<\/jats:italic> acts as the underlying mechanism.<\/jats:p>","DOI":"10.3389\/fgene.2021.786294","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T10:12:10Z","timestamp":1639735930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Microhomology-Mediated Nonhomologous End Joining Caused Rearrangement of EMD and FLNA in Emery-Dreifuss Muscular Dystrophy"],"prefix":"10.3389","volume":"12","author":[{"given":"Danyu","family":"Song","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1016\/B978-0-444-59565-2.00007-1","article-title":"Emery-dreifuss Muscular Dystrophy, Laminopathies, and Other Nuclear Envelopathies","volume":"113","author":"Bonne","year":"2013","journal-title":"Handb Clin. 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