{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T13:51:03Z","timestamp":1770040263321,"version":"3.49.0"},"reference-count":27,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"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":["336-13(196-DEFI\/285-CES"],"award-info":[{"award-number":["336-13(196-DEFI\/285-CES"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>While in most patients the identification of genetic alterations causing dystrophinopathies is a relatively straightforward task, a significant number require genomic and transcriptomic approaches that go beyond a routine diagnostic set-up. In this work, we present a Becker Muscular Dystrophy patient with elevated creatinine kinase levels, progressive muscle weakness, mild intellectual disability and a muscle biopsy showing dystrophic features and irregular dystrophin labelling. Routine molecular techniques (Southern-blot analysis, multiplex PCR, MLPA and genomic DNA sequencing) failed to detect a defect in the DMD gene. Muscle DMD transcript analysis (RT-PCR and cDNA-MLPA) showed the absence of exons 75 to 79, seen to be present at the genomic level. These results prompted the application of low-coverage linked-read whole-genome sequencing (WGS), revealing a possible rearrangement involving DMD intron 74 and a region located upstream of the PRDX4 gene. Breakpoint PCR and Sanger sequencing confirmed the presence of a ~8 Mb genomic inversion. Aberrant DMD transcripts were subsequently identified, some of which contained segments from the region upstream of PRDX4. Besides expanding the mutational spectrum of the disorder, this study reinforces the importance of transcript analysis in the diagnosis of dystrophinopathies and shows how WGS has a legitimate role in clinical laboratory genetics.<\/jats:p>","DOI":"10.3390\/ijms23010059","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T01:08:09Z","timestamp":1640135289000},"page":"59","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Integrating Whole-Genome Sequencing in Clinical Genetics: A Novel Disruptive Structural Rearrangement Identified in the Dystrophin Gene (DMD)"],"prefix":"10.3390","volume":"23","author":[{"given":"Ana","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Unidade de Gen\u00e9tica Molecular, Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto Magalh\u00e3es, Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS) e Laborat\u00f3rio Para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR), Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Ana","family":"Fortuna","sequence":"additional","affiliation":[{"name":"Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS) e Laborat\u00f3rio Para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR), Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Unidade de Gen\u00e9tica M\u00e9dica, Centro de Gen\u00e9tica M\u00e9dica Douto Jacinto Magalh\u00e3es, Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"}]},{"given":"Yavuz","family":"Ariyurek","sequence":"additional","affiliation":[{"name":"Leiden Genome Technology Center, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2437-2004","authenticated-orcid":false,"given":"M\u00e1rcia E.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Molecular, Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto Magalh\u00e3es, Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS) e Laborat\u00f3rio Para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR), Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Goreti","family":"Nadais","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Neurologia, Centro Hospitalar de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Jorge","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Anatomia Patol\u00f3gica, Centro Hospitalar de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Johan T.","family":"den Dunnen","sequence":"additional","affiliation":[{"name":"Leiden Genome Technology Center, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Departments of Human Genetics and Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-3290","authenticated-orcid":false,"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) e Laborat\u00f3rio Para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR), 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"}]},{"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 Doutor Jacinto Magalh\u00e3es, Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS) e Laborat\u00f3rio Para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR), Universidade do Porto, 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 Doutor Jacinto Magalh\u00e3es, Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS) e Laborat\u00f3rio Para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR), Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/humu.22758","article-title":"The TREAT-NMD DMD Global Database: Analysis of More than 7000 Duchenne Muscular Dystrophy 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