{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T10:15:47Z","timestamp":1778840147961,"version":"3.51.4"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,9,10]],"date-time":"2012-09-10T00:00:00Z","timestamp":1347235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2013,5]]},"abstract":"Arrhythmogenic right ventricular cardiomyopathy (ARVC<\/jats:styled-content>) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC<\/jats:styled-content>, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA<\/jats:styled-content> sequencing. We describe two cases of ARVC<\/jats:styled-content> possessing large deletions involving plakophilin\u20102 (PKP2<\/jats:styled-content><\/jats:italic>) identified with microarray analysis and\/or multiplex ligation\u2010dependent probe amplification (MLPA<\/jats:styled-content>) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2<\/jats:styled-content><\/jats:italic> excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA<\/jats:styled-content> analysis of PKP2<\/jats:styled-content><\/jats:italic> revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo<\/jats:italic> 7.9\u2009Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC<\/jats:styled-content> cases without clear disease causing mutations following initial sequencing analysis.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2012.01950.x","type":"journal-article","created":{"date-parts":[[2012,8,13]],"date-time":"2012-08-13T12:01:29Z","timestamp":1344859289000},"page":"452-456","source":"Crossref","is-referenced-by-count":37,"title":["Detection of genomic deletions of PKP2<\/scp><\/i> in arrhythmogenic right ventricular cardiomyopathy"],"prefix":"10.1111","volume":"83","author":[{"given":"JD","family":"Roberts","sequence":"first","affiliation":[{"name":"Inherited Arrhythmia Clinic and the Arrhythmia Research Laboratory University of Ottawa Heart Institute Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JC","family":"Herkert","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Groningen University of Groningen Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Rutberg","sequence":"additional","affiliation":[{"name":"Inherited Arrhythmia Clinic and the Arrhythmia Research Laboratory University of Ottawa Heart Institute Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SM","family":"Nikkel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Children's Hospital of Eastern Ontario University of Ottawa Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ACP","family":"Wiesfeld","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen University of Groningen Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Dooijes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RM","family":"Gow","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Inherited Arrhythmia Clinic The Childrens Hospital of Eastern Ontario Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JP","family":"van Tintelen","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Groningen University of Groningen Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MH","family":"Gollob","sequence":"additional","affiliation":[{"name":"Inherited Arrhythmia Clinic and the Arrhythmia Research Laboratory University of Ottawa Heart Institute Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,9,10]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio1182"},{"key":"e_1_2_4_3_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1136\/hrt.71.3.215","article-title":"Diagnosis of arrhythmogenic right ventricular dysplasia\/cardiomyopathy. Task Force of the working group myocardial and pericardial disease of the European Society of Cardiology and of the scientific council on cardiomyopathies of the International Society and Federation of Cardiology","volume":"71","author":"McKenna WJ","year":"1994","journal-title":"Br Heart J"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.840827"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2010.12.078"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.12.036"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01623.x"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2009.07.041"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.005405"},{"key":"e_1_2_4_10_1","article-title":"Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy","author":"Zwaag PA","year":"2012","journal-title":"Eur J Heart Fail"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.976936"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2028"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20035"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.988287"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34101"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-0004.2012.01950.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-0004.2012.01950.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T09:28:08Z","timestamp":1700645288000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-0004.2012.01950.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,10]]},"references-count":14,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1111\/j.1399-0004.2012.01950.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-0004.2012.01950.x","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,10]]}}}