{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T09:14:42Z","timestamp":1764494082070,"version":"3.41.2"},"reference-count":11,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1C1B5014840"],"award-info":[{"award-number":["2017R1C1B5014840"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011512","name":"National Research Foundation","doi-asserted-by":"publisher","award":["2017R1C1B5014840"],"award-info":[{"award-number":["2017R1C1B5014840"]}],"id":[{"id":"10.13039\/100011512","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Early\u2010onset myopathies show a wide spectrum of phenotypes and are composed of various types of inherited neuromuscular diseases, making it difficult to diagnose. <jats:italic>TTN<\/jats:italic> mutation\u2010related myopathy is a known cause of early\u2010onset myopathy. Since a next\u2010generation sequencing (NGS) has enabled sequencing of the vast amount of DNA, <jats:italic>TTN<\/jats:italic>, which is the longest coding sequence of any human gene, mutations can now be revealed. We report a 10\u2010year\u2010old female with severe congenital muscular weakness and delayed motor development since birth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Next\u2010generation sequencing as well as electromyography and muscle biopsy were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>To date, she is incapable of walking alone. Her younger sister had similar but more severe symptoms with respiratory failure. In electromyography, short\u2010duration, small\u2010amplitude motor unit action potential, and early recruitment patterns were observed in the involved proximal muscles, suggesting myopathy. Muscle histopathology showed a specific atrophy of increased fiber size variability, frequent nuclear internalization, as well as degeneration and regeneration of fibers with type I fiber predominance,\u00a0consistent with the findings of a previous report about congenital titinopathy. A NGS study revealed two different possible pathogenic variants in <jats:italic>TTN<\/jats:italic>: (a) canonical splicing mutation in the intron 105 (c. 29963\u20101G&gt;C) and (b) frameshift and truncating mutation in the exon 339 (c.92812dup\/p.Arg30938LysfsTer15). All variants were confirmed by conventional Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We propose that unbiased genomic sequencing can be helpful in screening patients with early\u2010onset myopathy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.866","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T04:28:12Z","timestamp":1563856092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Two novel mutations in <i>TTN<\/i> of a patient with congenital myopathy: A case report"],"prefix":"10.1002","volume":"7","author":[{"given":"Joon Young","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulhyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-084X","authenticated-orcid":false,"given":"Dae\u2010Hyun","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine College of Medicine, The Catholic University of Korea Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ja\u2010Hyun","family":"Jang","sequence":"additional","affiliation":[{"name":"Green Cross Genome Yongin Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3299-3038","authenticated-orcid":false,"given":"Ju Seok","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh2301.100981"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/342380"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.06.013"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.0168"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00076"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25241"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-304728"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.4899"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880141103"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(92)90249-K"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.866","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.866","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.866","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T07:04:49Z","timestamp":1692601489000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,22]]},"references-count":11,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1002\/mgg3.866"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.866","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2019,7,22]]},"assertion":[{"value":"2019-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e866"}}