{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:43:59Z","timestamp":1791431039706,"version":"4.3.3"},"reference-count":19,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T00:00:00Z","timestamp":1662508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>X-linked myotubular myopathy (XLMTM) is a severe form of centronuclear myopathy, characterized by generalized weakness and respiratory insufficiency, associated with pathogenic variants in the MTM1 gene. NGS targeted sequencing on the DNA of a three-month-old child affected by XLMTM identified the novel hemizygous MTM1 c.1261-5T&gt;G intronic variant, which interferes with the normal splicing process, generating two different abnormal transcripts simultaneously expressed in the patient\u2019s muscular cells. The first aberrant transcript, induced by the activation of a cryptic splice site in intron 11, includes four intronic nucleotides upstream of exon 12, resulting in a shift in the transcript reading frame and introducing a new premature stop codon in the catalytic domain of the protein (p.Arg421SerfsTer7). The second aberrant MTM1 transcript, due to the lack of recognition of the 3\u2032 acceptor splice site of intron 11 from the spliceosome complex, leads to the complete skipping of exon 12. We expanded the genotypic spectrum of XLMTM underlying the importance of intron\u2013exons boundaries sequencing in male patients affected by XLMTM.<\/jats:p>","DOI":"10.3390\/ijms231810274","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T20:52:03Z","timestamp":1662583923000},"page":"10274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel Splicing Mutation in MTM1 Leading to Two Abnormal Transcripts Causes Severe Myotubular Myopathy"],"prefix":"10.3390","volume":"23","author":[{"given":"Luca","family":"Bosco","sequence":"first","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Viale S. Paolo 15, 00146 Rome, Italy"},{"name":"Department of Science, University \u201cRoma Tre\u201d, Viale Marconi 446, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Leone","sequence":"additional","affiliation":[{"name":"Centro Clinico Nemo, Fondazione Policlinico Universitario A. Gemelli IRCCS-Universit\u00e0 Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00146 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1180-8772","authenticated-orcid":false,"given":"Laura","family":"Costa Comellas","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Vall d\u2019Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d\u2019Hebron, Vall d\u2019Hebron Barcelona Hospital Campus, Passeig de la Vall d\u2019Hebron, 119-129, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4327-6969","authenticated-orcid":false,"given":"Mauro","family":"Monforte","sequence":"additional","affiliation":[{"name":"UOC di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Pane","sequence":"additional","affiliation":[{"name":"Centro Clinico Nemo, Fondazione Policlinico Universitario A. Gemelli IRCCS-Universit\u00e0 Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00146 Roma, Italy"},{"name":"Pediatric Neurology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS-Universit\u00e0 Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Centro Clinico Nemo, Fondazione Policlinico Universitario A. Gemelli IRCCS-Universit\u00e0 Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00146 Roma, Italy"},{"name":"Pediatric Neurology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS-Universit\u00e0 Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-4590","authenticated-orcid":false,"given":"Enrico","family":"Bertini","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Viale S. Paolo 15, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Viale S. Paolo 15, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1820-8489","authenticated-orcid":false,"given":"Fabiana","family":"Fattori","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Viale S. Paolo 15, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1007\/s00415-015-7757-9","article-title":"Centronuclear myopathies: Genotype\u2013phenotype correlation and frequency of defined genetic forms in an Italian cohort","volume":"262","author":"Fattori","year":"2015","journal-title":"J. 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