{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T19:49:07Z","timestamp":1760644147479,"version":"3.41.2"},"reference-count":8,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T00:00:00Z","timestamp":1567641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006928","name":"Ohio State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006928","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pathogenic variants in <jats:italic>TTN (OMIM 188840),<\/jats:italic> encoding the largest human protein, are known to cause dilated cardiomyopathy and several forms of skeletal myopathy. The clinical interpretation of <jats:italic>TTN<\/jats:italic> variants is challenging, however, due to the frequency of missense changes, variable testing and reporting practices in commercial laboratories, and incomplete understanding of the spectrum of <jats:italic>TTN\u2010<\/jats:italic>related disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report a heterozygous <jats:italic>TTN<\/jats:italic> deletion segregating in a family with an unusual skeletal myopathy phenotype associated with facial weakness, gait abnormality, and dilated cardiomyopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel 16.430\u00a0kb heterozygous deletion spanning part of the A\u2010 and M\u2010bands of <jats:italic>TTN<\/jats:italic> was identified in the proband and his symptomatic son, as well as in an additional son whose symptoms were identified on clinical evaluation. The deletion was found to be de novo in the proband.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Pathogenic variants in <jats:italic>TTN<\/jats:italic> may be an unrecognized cause of skeletal myopathy phenotypes, particularly when accompanied by dilated cardiomyopathy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.924","type":"journal-article","created":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T00:15:03Z","timestamp":1567728903000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A novel <i>TTN<\/i> deletion in a family with skeletal myopathy, facial weakness, and dilated cardiomyopathy"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6583-9996","authenticated-orcid":false,"given":"Jennifer","family":"Roggenbuck","sequence":"first","affiliation":[{"name":"The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Rich","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Morales","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A.","family":"Tan","sequence":"additional","affiliation":[{"name":"Invitae Corporation San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Eck","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"King","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Vatta","sequence":"additional","affiliation":[{"name":"Invitae Corporation San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Winder","sequence":"additional","affiliation":[{"name":"Invitae Corporation San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bakri","family":"Elsheikh","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ray E.","family":"Hershberger","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"Kissel","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,9,5]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_8_2_1","DOI":"10.1212\/WNL.0b013e3182a6ca62"},{"doi-asserted-by":"publisher","key":"e_1_2_8_3_1","DOI":"10.1093\/hmg\/ddt494"},{"doi-asserted-by":"publisher","key":"e_1_2_8_4_1","DOI":"10.1002\/ana.24102"},{"doi-asserted-by":"publisher","key":"e_1_2_8_5_1","DOI":"10.1086\/342380"},{"doi-asserted-by":"publisher","key":"e_1_2_8_6_1","DOI":"10.1038\/nature19057"},{"doi-asserted-by":"publisher","key":"e_1_2_8_7_1","DOI":"10.1016\/j.jmoldx.2015.04.009"},{"volume-title":"GeneReviews\u00ae","year":"1993","author":"Pfeffer G.","key":"e_1_2_8_8_1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_9_1","DOI":"10.3233\/JND-160158"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.924","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.924","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.924","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T07:19:28Z","timestamp":1708759168000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,5]]},"references-count":8,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1002\/mgg3.924"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.924","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2019,9,5]]},"assertion":[{"value":"2019-05-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e924"}}