{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:47:38Z","timestamp":1790254058907,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The French Muscular Dystrophy Association (AFM-T\u00e9l\u00e9thon)","award":["AFM 21381"],"award-info":[{"award-number":["AFM 21381"]}]},{"name":"The French Muscular Dystrophy Association (AFM-T\u00e9l\u00e9thon)","award":["AFM 24259"],"award-info":[{"award-number":["AFM 24259"]}]},{"name":"The French Muscular Dystrophy Association (AFM-T\u00e9l\u00e9thon)","award":["AFM 22734"],"award-info":[{"award-number":["AFM 22734"]}]},{"name":"D\u00e9l\u00e9gation \u00e0 la Recherche Clinique et \u00e0 l\u2019Innovation du Groupement de Coop\u00e9ration Sanitaire de la Mission d\u2019Enseignement, de Recherche, de R\u00e9f\u00e9rence, et d\u2019Innovation (DRCI-GCS-MERRI) de Montpellier\u2013N\u00eemes","award":["AFM 21381"],"award-info":[{"award-number":["AFM 21381"]}]},{"name":"D\u00e9l\u00e9gation \u00e0 la Recherche Clinique et \u00e0 l\u2019Innovation du Groupement de Coop\u00e9ration Sanitaire de la Mission d\u2019Enseignement, de Recherche, de R\u00e9f\u00e9rence, et d\u2019Innovation (DRCI-GCS-MERRI) de Montpellier\u2013N\u00eemes","award":["AFM 24259"],"award-info":[{"award-number":["AFM 24259"]}]},{"name":"D\u00e9l\u00e9gation \u00e0 la Recherche Clinique et \u00e0 l\u2019Innovation du Groupement de Coop\u00e9ration Sanitaire de la Mission d\u2019Enseignement, de Recherche, de R\u00e9f\u00e9rence, et d\u2019Innovation (DRCI-GCS-MERRI) de Montpellier\u2013N\u00eemes","award":["AFM 22734"],"award-info":[{"award-number":["AFM 22734"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital titinopathies reported to date show autosomal recessive inheritance and are caused by a variety of genomic variants, most of them located in metatranscript (MTT)-only exons. The aim of this study was to describe additional patients and establish robust genotype\u2013phenotype associations in titinopathies. This study involved analyzing molecular, clinical, pathological, and muscle imaging features in 20 patients who had at least one pathogenic or likely pathogenic TTN variant in MTT-only exons, with onset occurring antenatally or in the early postnatal stages. The 20 patients with recessive inheritance exhibited a heterogeneous range of phenotypes. These included fetal lethality, progressive weakness, cardiac or respiratory complications, hyper-CKemia, or dystrophic muscle biopsies. MRI revealed variable abnormalities in different muscles. All patients presented severe congenital myopathy at birth, characterized by arthrogryposis (either multiplex or axial\u2013distal) or neonatal hypotonia in most cases. This study provides detailed genotype\u2013phenotype correlations in congenital titinopathies caused by mutations in MTT-only exons. The findings highlight the variability in clinical presentation and the severity of phenotypes associated with these specific genetic alterations. RNA-seq analyses provided valuable insights into the molecular consequences of TTN variants, particularly in relation to splicing defects and nonsense-mediated RNA decay. In conclusion, this study reinforces the genotype\u2013phenotype correlations between congenital myopathies and variants in TTN MTT-only exons, improves their molecular diagnosis, and provides a better understanding of their pathophysiology.<\/jats:p>","DOI":"10.3390\/ijms252312994","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T09:18:32Z","timestamp":1733217512000},"page":"12994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Congenital Titinopathies Linked to Mutations in TTN Metatranscript-Only Exons"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5895-3064","authenticated-orcid":false,"given":"Aur\u00e9lien","family":"Perrin","sequence":"first","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, Centre Hospitalier Universitaire de Montpellier, 34093 Montpellier, France"},{"name":"PhyMedExp, INSERM, CNRS, Universit\u00e9 de Montpellier, 34093 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocio","family":"Garcia-Uzquiano","sequence":"additional","affiliation":[{"name":"AP-HP, GHU Universit\u00e9 Paris-Saclay, Neuromuscular Center, Child Neurology and ICU Department, Raymond Poincare Hospital, 92380 Garches, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Stojkovic","sequence":"additional","affiliation":[{"name":"AP-HP, Centre de R\u00e9f\u00e9rence des Maladies Neuromusculaires Nord\/Est\/\u00cele-de-France, Sorbonne Universit\u00e9, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Tard","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Neurologie et des Troubles du Mouvement, U1172, Centre Hospitalo Universitaire (CHU) de Lille, CT, Centre de R\u00e9f\u00e9rence des Maladies Neuromusculaires Nord\/Est\/\u00cele-de-France, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-2662","authenticated-orcid":false,"given":"Corinne","family":"Metay","sequence":"additional","affiliation":[{"name":"AP-HP, UF Molecular Cardiogenetics and Myogenetics, Sorbonne Universit\u00e9 and Sorbonne Universit\u00e9 UPMC Paris 06, Inserm UMRS974, Research Center in Myology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bergougnoux","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, Centre Hospitalier Universitaire de Montpellier, 34093 Montpellier, France"},{"name":"PhyMedExp, INSERM, CNRS, Universit\u00e9 de Montpellier, 34093 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Van 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U1251, Aix-Marseille Universit\u00e9, 13385 Marseille, France"},{"name":"D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital Timone Enfants, APHM, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Juntas-Morales","sequence":"additional","affiliation":[{"name":"Neurology Department, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Titin\u2019s Network Collaborators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Koenig","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, Centre Hospitalier Universitaire de Montpellier, 34093 Montpellier, France"},{"name":"PhyMedExp, INSERM, CNRS, Universit\u00e9 de Montpellier, 34093 Montpellier, 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