{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:02:18Z","timestamp":1753869738459,"version":"3.41.2"},"reference-count":7,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T00:00:00Z","timestamp":1569801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy (LVH) in the absence of predisposing cardiovascular conditions. Pathogenic variants in at least 16 cardiac sarcomeric genes have been implicated in HCM, most of which act in a dominant\u2010negative fashion. However loss\u2010of\u2010function (haploinsufficiency) is the most common disease mechanism for pathogenic variants in <jats:italic>MYBPC3<\/jats:italic>, suggesting that <jats:italic>MYBPC3<\/jats:italic> complete deletion may play a role in HCM pathogenesis. Here, we investigate <jats:italic>MYBPC3<\/jats:italic> complete deletion as a disease mechanism in HCM by analyzing two unrelated patients with confirmed diagnosis of HCM that tested negative by Sanger sequencing analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>MYBPC3<\/jats:italic> complete deletion was investigated by Multiplex ligation\u2010dependent probe amplification (MLPA) and microarray analyses. The mechanism of deletion was investigated by interrogating the SINEBase database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patient\u20101 was diagnosed with nonobstructive HCM in his mid\u201040s while undergoing assessment for palpitations, and patient\u20102 with obstructive HCM in his late\u201020s while undergoing systolic heart murmur assessment for an unrelated illness. MLPA testing revealed a heterozygous deletion of all <jats:italic>MYBPC3<\/jats:italic> exons in both patients. Subsequent microarray testing confirmed these deletions which extended beyond the 5\u2032 and 3\u2032 ends of <jats:italic>MYBPC3<\/jats:italic>. Genomic assessment suggested that these deletions resulted from <jats:italic>Alu\/Alu<\/jats:italic>\u2010homologous recombination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that haploinsufficiency resulting from <jats:italic>MYBPC3<\/jats:italic> complete deletion, potentially mediated by <jats:italic>Alu<\/jats:italic> recombination, is an important disease mechanism in cardiomyopathy and emphasizes the importance of copy number variation analysis in patients clinically suspected of HCM.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.951","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T05:30:06Z","timestamp":1569907806000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>ALU<\/i> transposition induces familial hypertrophic cardiomyopathy"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-2545","authenticated-orcid":false,"given":"Landry","family":"Nfonsam","sequence":"first","affiliation":[{"name":"CHEO Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijia","family":"Huang","sequence":"additional","affiliation":[{"name":"CHEO Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Carson","sequence":"additional","affiliation":[{"name":"CHEO Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"McGowan\u2010Jordan","sequence":"additional","affiliation":[{"name":"CHEO Ottawa Canada"},{"name":"University of Ottawa Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Beaulieu Bergeron","sequence":"additional","affiliation":[{"name":"CHEO Ottawa Canada"},{"name":"University of Ottawa Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharan","family":"Goobie","sequence":"additional","affiliation":[{"name":"Dalhousie University Halifax Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Conacher","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre London Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"McCarty","sequence":"additional","affiliation":[{"name":"Western University London Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Benson","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacy","family":"Hewson","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Zahavich","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Sinclair\u2010Bourque","sequence":"additional","affiliation":[{"name":"CHEO Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Smith","sequence":"additional","affiliation":[{"name":"CHEO Ottawa Canada"},{"name":"University of Ottawa Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Potter","sequence":"additional","affiliation":[{"name":"CHEO Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahdi","family":"Ghani","sequence":"additional","affiliation":[{"name":"CHEO Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Bronicki","sequence":"additional","affiliation":[{"name":"CHEO Ottawa Canada"},{"name":"University of Ottawa Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Jarinova","sequence":"additional","affiliation":[{"name":"CHEO Ottawa Canada"},{"name":"University of Ottawa Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,9,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp247"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2012.01.002"},{"volume-title":"GeneReviews","year":"2008","author":"Cirino A. L.","key":"e_1_2_7_4_1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.10.001"},{"key":"e_1_2_7_6_1","unstructured":"OMIM. (2019).Online Mendelian Inheritance in Man OMIM.Baltimore MD:McKusick-Nathans Institute of Genetic Medicine Johns Hopkins University. Retrieved fromhttps:\/\/omim.org\/"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36363"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1263"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.951","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.951","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.951","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T13:56:24Z","timestamp":1692626184000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,30]]},"references-count":7,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/mgg3.951"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.951","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2019,9,30]]},"assertion":[{"value":"2019-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e951"}}