{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:51:49Z","timestamp":1779141109334,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,8,21]],"date-time":"2017-08-21T00:00:00Z","timestamp":1503273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009729","name":"Ludwig Institute for Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009729","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005294","name":"Massachusetts General Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005294","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":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nemaline myopathy (<jats:styled-content style=\"fixed-case\">NEM<\/jats:styled-content>) is one of the three major forms of congenital myopathy and is characterized by diffuse muscle weakness, hypotonia, respiratory insufficiency, and the presence of nemaline rod structures on muscle biopsy. Mutations in troponin T1 (<jats:italic><jats:styled-content style=\"fixed-case\">TNNT<\/jats:styled-content>1<\/jats:italic>) is 1 of 10 genes known to cause <jats:styled-content style=\"fixed-case\">NEM<\/jats:styled-content>. To date, only homozygous nonsense mutations or compound heterozygous truncating or internal deletion mutations in <jats:italic><jats:styled-content style=\"fixed-case\">TNNT<\/jats:styled-content>1<\/jats:italic> gene have been identified in <jats:styled-content style=\"fixed-case\">NEM<\/jats:styled-content>. This extended family is of historical importance as some members were reported in the 1960s as initial evidence that <jats:styled-content style=\"fixed-case\">NEM<\/jats:styled-content> is a hereditary disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Proband and extended family underwent Sanger sequencing for <jats:italic><jats:styled-content style=\"fixed-case\">TNNT<\/jats:styled-content>1<\/jats:italic>. We performed <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and immunoblot on muscle to assess <jats:italic><jats:styled-content style=\"fixed-case\">TNNT<\/jats:styled-content>1 <\/jats:italic><jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression and protein levels in proband and father.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report a novel heterozygous missense mutation of <jats:italic><jats:styled-content style=\"fixed-case\">TNNT<\/jats:styled-content>1<\/jats:italic> c.311A&gt;T (p.E104V) that segregated in an autosomal dominant fashion in a large family residing in the United States. Extensive sequencing of the other known genes for <jats:styled-content style=\"fixed-case\">NEM<\/jats:styled-content> failed to identify any other mutant alleles. Muscle biopsies revealed a characteristic pattern of nemaline rods and severe myofiber hypotrophy that was almost entirely restricted to the type 1 fiber population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This novel mutation alters a residue that is highly conserved among vertebrates. This report highlights not only a family with autosomal dominant inheritance of <jats:styled-content style=\"fixed-case\">NEM<\/jats:styled-content>, but that this novel mutation likely acts via a dominant negative mechanism.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.325","type":"journal-article","created":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T04:18:51Z","timestamp":1503375531000},"page":"678-691","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Novel autosomal dominant <i><scp>TNNT<\/scp>1<\/i> mutation causing nemaline myopathy"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5676-7516","authenticated-orcid":false,"given":"Chamindra G.","family":"Konersman","sequence":"first","affiliation":[{"name":"Department of Neurosciences University of California San Diego San Diego California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernande","family":"Freyermuth","sequence":"additional","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts"},{"name":"Broad Institute of Harvard University and MIT Cambridge Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas L.","family":"Winder","sequence":"additional","affiliation":[{"name":"Prevention Genetics Marshfield Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W.","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pathology Department of Pathology and Laboratory Medicine and Neuroscience Research Center Medical College of Wisconsin Milwaukee Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clotilde","family":"Lagier\u2010Tourenne","sequence":"additional","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts"},{"name":"Broad Institute of Harvard University and MIT Cambridge Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shailendra B.","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Metabolism and Clinical Nutrition Medical College of Wisconsin, and Clement J. 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