{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:34:15Z","timestamp":1760402055858,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:00:00Z","timestamp":1579564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/SAU-GMG\/117046\/2010","SFRH\/BPD\/101965\/2014","SFRH\/BD\/124372\/2016"],"award-info":[{"award-number":["PTDC\/SAU-GMG\/117046\/2010","SFRH\/BPD\/101965\/2014","SFRH\/BD\/124372\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"N2020","award":["NORTE2020\/DESVENDAR\/DGH\/jn2016"],"award-info":[{"award-number":["NORTE2020\/DESVENDAR\/DGH\/jn2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Here, we present the molecular diagnosis of a patient with a general clinical suspicion of Mucopolysaccharidosis, highlighting the different tools used to perform its molecular characterization. In order to decrease the turnaround time for the final report and contribute to reduce the \u201cdiagnostic odyssey\u201d, which frequently afflicts affected families, the proband\u2019s sample was simultaneously screened for mutations in a number of lysosomal function-related genes with targeted next-generation sequencing (NGS) protocol. After variant calling, the most probable cause for disease was a novel ARSB intronic variant, c.1213+5G&gt;T [IVS6+5G&gt;T], detected in homozygosity. In general, homozygous or compound heterozygous mutations in the ARSB gene, underlie MPS type VI or Maroteaux-Lamy syndrome. Still, even though the novel c.1213+5G&gt;T variant was easy to detect by both NGS and Sanger sequencing, only through indirect studies and functional analyses could we present proof of principle on its pathogenicity. Globally, this case reminds us that whenever a novel variant is detected, its pathogenicity must be carefully assessed before a definitive diagnosis is established, while highlighting alternative approaches that may be used to assess its effect in the absence RNA\/cDNA sample(s) from the proband. This is particularly relevant for intronic variants such as the one here reported. Special attention will be given to the use of reporter minigene systems, which may be constructed\/designed to dissect the effect of this sort of alterations, providing an insight into their consequences over the normal pre-mRNA splicing process of the affected gene.<\/jats:p>","DOI":"10.3390\/diagnostics10020058","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T11:25:59Z","timestamp":1579605959000},"page":"58","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Molecular Characterization of a Novel Splicing Mutation Underlying Mucopolysaccharidosis (MPS) Type VI\u2014Indirect Proof of Principle on Its Pathogenicity"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2222-3622","authenticated-orcid":false,"given":"Maria Francisca","family":"Coutinho","sequence":"first","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, 55142, 4051-401 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3726-2851","authenticated-orcid":false,"given":"Marisa","family":"Encarna\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, 55142, 4051-401 Porto, Portugal"},{"name":"Newborn Screening, Metabolism and Genetics Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"}]},{"given":"Liliana","family":"Matos","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, 55142, 4051-401 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7125-8488","authenticated-orcid":false,"given":"Lisbeth","family":"Silva","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"},{"name":"Newborn Screening, Metabolism and Genetics Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"}]},{"given":"Diogo","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, 55142, 4051-401 Porto, Portugal"}]},{"given":"Juliana In\u00eas","family":"Santos","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"},{"name":"Biology Department, Faculty of Sciences, University of Porto, 4150-179 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-1028","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Prata","sequence":"additional","affiliation":[{"name":"Biology Department, Faculty of Sciences, University of Porto, 4150-179 Porto, Portugal"},{"name":"i3S\u2014Health Research and Innovation Institute, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Laura","family":"Vilarinho","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, 55142, 4051-401 Porto, Portugal"},{"name":"Newborn Screening, Metabolism and Genetics Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"}]},{"given":"Sandra","family":"Alves","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, INSA, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, 55142, 4051-401 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41572-018-0037-0","article-title":"Author Correction: Lysosomal storage diseases","volume":"4","author":"Platt","year":"2018","journal-title":"Nat. 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