{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:27:15Z","timestamp":1776212835905,"version":"3.50.1"},"reference-count":23,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:00:00Z","timestamp":1506988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundo para a Investiga\u00e7\u00e3o e Desenvolvimento do Centro Hospitalar do Porto","award":["Grant ref.: 336-13(196-DEFI\/285-CES)"],"award-info":[{"award-number":["Grant ref.: 336-13(196-DEFI\/285-CES)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>A broad mutational spectrum in the dystrophin (DMD) gene, from large deletions\/duplications to point mutations, causes Duchenne\/Becker muscular dystrophy (D\/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced dystrophin labeling, where multiplex-ligation probe amplification (MLPA) and genomic sequencing failed to detect pathogenic variants. Bioinformatic, transcriptomic (real time PCR, RT-PCR), and genomic approaches (Southern blot, long-range PCR, and single molecule real-time sequencing) were used to characterize the mutation. An aberrant transcript was identified, containing a 103-nucleotide insertion between exons 51 and 52, with no similarity with the DMD gene. This corresponded to the partial exonization of a long interspersed nuclear element (LINE-1), disrupting the open reading frame. Further characterization identified a complete LINE-1 (~6 kb with typical hallmarks) deeply inserted in intron 51. Haplotyping and segregation analysis demonstrated that the mutation had a de novo origin. Besides underscoring the importance of mRNA studies in genetically unsolved cases, this is the first report of a disease-causing fully intronic LINE-1 element in DMD, adding to the diversity of mutational events that give rise to D\/BMD.<\/jats:p>","DOI":"10.3390\/genes8100253","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T11:33:30Z","timestamp":1507030410000},"page":"253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin Gene"],"prefix":"10.3390","volume":"8","author":[{"given":"Ana","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Unidade de Gen\u00e9tica Molecular, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es, Centro Hospitalar do Porto, 4050-106 Porto, Portugal"},{"name":"Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3924-6385","authenticated-orcid":false,"given":"Jorge","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Molecular, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es, Centro Hospitalar do Porto, 4050-106 Porto, Portugal"},{"name":"Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Teresa","family":"Coelho","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Neurofisiologia, Departamento de Neuroci\u00eancias, Centro Hospitalar do Porto, 4099-001 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9260-0227","authenticated-orcid":false,"given":"Ricardo","family":"Taipa","sequence":"additional","affiliation":[{"name":"Unidade de Neuropatologia, Centro Hospitalar do Porto, 4099-001 Porto, Portugal"}]},{"given":"Manuel","family":"Melo-Pires","sequence":"additional","affiliation":[{"name":"Unidade de Neuropatologia, Centro Hospitalar do Porto, 4099-001 Porto, Portugal"}]},{"given":"M\u00e1rio","family":"Sousa","sequence":"additional","affiliation":[{"name":"Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Departamento de Microscopia, Laborat\u00f3rio de Biologia Celular, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Centro de Gen\u00e9tica da Reprodu\u00e7\u00e3o Prof. Alberto Barros, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8594-6377","authenticated-orcid":false,"given":"Ros\u00e1rio","family":"Santos","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Molecular, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es, Centro Hospitalar do Porto, 4050-106 Porto, Portugal"},{"name":"Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\/REQUIMTE, Departamento de Ci\u00eancias Biol\u00f3gicas, Laborat\u00f3rio de Bioqu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/ana.23528","article-title":"Evidence-based path to newborn screening for Duchenne muscular dystrophy","volume":"71","author":"Mendell","year":"2012","journal-title":"Ann. 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