{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:17:46Z","timestamp":1789874266658,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["339437"],"award-info":[{"award-number":["339437"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["346209"],"award-info":[{"award-number":["346209"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["361979"],"award-info":[{"award-number":["361979"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["101080874"],"award-info":[{"award-number":["101080874"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["230217"],"award-info":[{"award-number":["230217"]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Titin, the largest human protein, is essential for sarcomere structure and function. The\n                      <jats:italic>TTN<\/jats:italic>\n                      gene, spanning 364 exons, undergoes extensive alternative splicing thus producing multiple isoforms. The M\u2010band region, encoded by exons 359\u2013364, plays a critical role in sarcomere integrity and mechanical stability. Exon 363 is of interest due to its involvement in titinopathies. Pathogenic truncating variants in this exon have been linked to recessive myopathies, including and mainly young\u2010onset recessive distal titinopathy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A multicenter study was conducted on six patients from five unrelated families with confirmed recessive titinopathy and truncating variants in exon 363. Clinical evaluations were performed. Genetic testing and segregation analysis confirmed the phase of the variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel truncating variant c.107578C&gt;T, p.(Gln35860Ter) was identified in four unrelated patients of Eastern European ancestry, all carrying a second pathogenic variant in a canonical\n                      <jats:italic>TTN<\/jats:italic>\n                      exon. These patients exhibited juvenile\/young\u2010adult onset recessive distal titinopathy with progressive lower limb weakness, frequently asymmetric muscle involvement, and no cardiac or respiratory complications. A Belgian family presented with a congenital myopathy caused by a novel frameshift deletion c.107430delA, p.(Ser35811AlafsTer32) in exon 363, in compound heterozygosity with a truncating variant in exon 208. These patients showed a more severe phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study expands the spectrum of TTN\u2010related myopathies, emphasizing exon 363's pathogenic significance. Truncating exon 363 variants contribute to young onset recessive distal and sometimes early onset titinopathy with contractures, and the phenotype severity is influenced by the second variant's location and exon usage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70433","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T11:01:43Z","timestamp":1763377303000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Mutations in\n                    <i>Titin<\/i>\n                    Exon 363 With Different Phenotypes Including a Founder Mutation in Eastern Europe"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8670-744X","authenticated-orcid":false,"given":"Veronica","family":"Sian","sequence":"first","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Department of Medical and Clinical Genetics, Medicum University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francesca","family":"Di Feo","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Department of Medical and Clinical Genetics, Medicum University of Helsinki  Helsinki Finland"},{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health (DINOGMI) University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei","family":"Kurbatov","sequence":"additional","affiliation":[{"name":"Research Institute of Experimental Biology and Medicine Voronezh State Medical University N.N. Burdenko  Voronezh Russia"},{"name":"Department of Neurology Named After K.N. Tretyakov Saratov State Medical University Named After V.I. Razumovsky  Saratov Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vihola","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Laboratory of Genetics, HUS Diagnostic Center University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Luque","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Department of Medical and Clinical Genetics, Medicum University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fedor","family":"Konovalov","sequence":"additional","affiliation":[{"name":"Independent Clinical Bioinformatics Laboratory  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2979-556X","authenticated-orcid":false,"given":"Stojan","family":"Peric","sequence":"additional","affiliation":[{"name":"Neurology Clinic, University Clinical Center of Serbia, Faculty of Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathrina","family":"Duffy","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Center for Neurology University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Kornblum","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Center for Neurology University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-443X","authenticated-orcid":false,"given":"Kristl 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