{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:24:25Z","timestamp":1790713465017,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T00:00:00Z","timestamp":1487289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Rare Disease Foundation and BC Children's Hospital Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both ventricles. Among hereditary DCM, the genetic causes are heterogeneous, and include mutations encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium\u2010handling proteins. We report three severely affected males, in a four\u2010generation pedigree, with DCM phenotype who underwent cardiac transplant. Cardiomegaly with marked biventricular dilation and fibrosis were noticeable histopathological findings. The affected males had tested negative on a 46\u2010gene pancardiomyopathy panel. Whole Exome Sequencing (WES) was performed to reveal mutation in the gene responsible in generation of DCM phenotypes. The 1\u2010bp (Chr10:121435979delC; c.913delC) novel heterozygous deletion in exon 4 of <jats:italic>BAG3<\/jats:italic>, was identified in three affected males, resulted in frame\u2010shift and a premature termination codon (p.Met306\u2010Stop) producing a truncated BAG3 protein lacking functionally important PXXP and BAG domains. WES data were further utilized to map 10 SNP markers around the discovered mutation to generate shared disease haplotype in all affected individuals encompassing 11\u2009Mb on 10q25.3\u201326.2 harboring <jats:italic>BAG3<\/jats:italic>. Finally genotypes were inferred for the unavailable\/deceased individuals in the pedigrees. Here we propose that Chr10:121435979delC in <jats:italic>BAG3<\/jats:italic> is a causal mutation in these subjects. Our and earlier studies indicate that <jats:italic>BAG3<\/jats:italic> mutations are associated with DCM phenotypes. <jats:italic>BAG3<\/jats:italic> should be added to cardiomyopathy gene panels for screening of DCM patients, and patients previously considered gene elusive should undergo sequencing of the <jats:italic>BAG3<\/jats:italic> gene. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38087","type":"journal-article","created":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T13:51:08Z","timestamp":1487339468000},"page":"699-705","source":"Crossref","is-referenced-by-count":18,"title":["Whole exome sequencing identified 1 base pair novel deletion in BCL2\u2010associated athanogene 3 (BAG3) gene associated with severe dilated cardiomyopathy (DCM) requiring heart transplant in multiple family members"],"prefix":"10.1002","volume":"173","author":[{"given":"Muhammad Arshad","family":"Rafiq","sequence":"first","affiliation":[{"name":"Physiology and Experimental Medicine The Hospital for Sick Children and Research Institute Toronto Ontario Canada"},{"name":"Department of Bio\u2010Sciences COMSATS Institute of Information Technology (CIIT) Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayeshah","family":"Chaudhry","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics The Hospital for Sick Children University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Care","sequence":"additional","affiliation":[{"name":"Fred A. Litwin Family Center in Genetic Medicine University Health Network University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danna A.","family":"Spears","sequence":"additional","affiliation":[{"name":"Division of Cardiology University Health Network University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal F.","family":"Morel","sequence":"additional","affiliation":[{"name":"Fred A. Litwin Family Center in Genetic Medicine University Health Network University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Physiology and Experimental Medicine The Hospital for Sick Children and Research Institute Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907696107"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21603"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt106"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1093\/ejcts\/15.Supplement_1.S12","article-title":"Partial left ventriculectomy\u2014the Batista procedure","volume":"1","author":"Batista R","year":"1999","journal-title":"Eur J Cardiothorac Surg"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2014.09.030"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.80.3.564"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.8"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.5.14964"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2012.07.003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-12-192"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181f2481f"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.225649"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01659.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti009"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.01.013"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62862"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.15"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-013-0375-1"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.01.016"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00274-6"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a014894"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.23"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2011.24"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20865"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21553"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs191"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr105"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.38087","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38087","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T06:24:24Z","timestamp":1695536664000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,17]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1002\/ajmg.a.38087"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38087","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,17]]}}}