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Assessing Lysosomal Disorders in the NGS Era: Identification of Novel Rare Variants

2020-09-01Journal article Open access
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dc.contributor.authorEncarnação, Marisa
dc.contributor.authorCoutinho, Maria Francisca
dc.contributor.authorSilva, Lisbeth
dc.contributor.authorRibeiro, Diogo
dc.contributor.authorOuesleti, Souad
dc.contributor.authorCampos, Teresa
dc.contributor.authorSantos, Helena
dc.contributor.authorMartins, Esmeralda
dc.contributor.authorCardoso, Maria Teresa
dc.contributor.authorVilarinho, Laura
dc.contributor.authorAlves, Sandra
dc.date.accessioned2021-12-09T15:17:37Z
dc.date.available2021-12-09T15:17:37Z
dc.date.issued2020-09-01
dc.description.abstractLysosomal storage diseases (LSDs) are a heterogeneous group of genetic disorders with variable degrees of severity and a broad phenotypic spectrum, which may overlap with a number of other conditions. While individually rare, as a group LSDs affect a significant number of patients, placing an important burden on affected individuals and their families but also on national health care systems worldwide. Here, we present our results on the use of an in-house customized next-generation sequencing (NGS) panel of genes related to lysosome function as a first-line molecular test for the diagnosis of LSDs. Ultimately, our goal is to provide a fast and effective tool to screen for virtually all LSDs in a single run, thus contributing to decrease the diagnostic odyssey, accelerating the time to diagnosis. Our study enrolled a group of 23 patients with variable degrees of clinical and/or biochemical suspicion of LSD. Briefly, NGS analysis data workflow, followed by segregation analysis allowed the characterization of approximately 41% of the analyzed patients and the identification of 10 different pathogenic variants, underlying nine LSDs. Importantly, four of those variants were novel, and, when applicable, their effect over protein structure was evaluated through in silico analysis. One of the novel pathogenic variants was identified in the GM2A gene, which is associated with an ultra-rare (or misdiagnosed) LSD, the AB variant of GM2 Gangliosidosis. Overall, this case series highlights not only the major advantages of NGS-based diagnostic approaches but also, to some extent, its limitations ultimately promoting a reflection on the role of targeted panels as a primary tool for the prompt characterization of LSD patients.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEncarnação M, Coutinho MF, Silva L, et al. Assessing Lysosomal Disorders in the NGS Era: Identification of Novel Rare Variants. Int J Mol Sci. 2020;21(17):6355. doi:10.3390/ijms21176355pt_PT
dc.identifier.doi10.3390/ijms21176355pt_PT
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/10400.16/2650
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation.publisherversionhttps://www.mdpi.com/1422-0067/21/17/6355pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCLN7pt_PT
dc.subjectGM2 Gangliosidosispt_PT
dc.subjectGM2A genept_PT
dc.subjectbioinformatics analysispt_PT
dc.subjectdiagnostics odysseypt_PT
dc.subjectlysosomal storage diseases (LSDs)pt_PT
dc.subjectmolecular genetic testing (MGT)pt_PT
dc.subjectnext-generation sequencing (NGS)pt_PT
dc.titleAssessing Lysosomal Disorders in the NGS Era: Identification of Novel Rare Variantspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceSwitzerlandpt_PT
oaire.citation.issue17pt_PT
oaire.citation.startPage6355pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume21pt_PT
person.familyNameMartins
person.givenNameEsmeralda
person.identifier.ciencia-idBF1C-DAE5-FAEA
person.identifier.orcid0000-0002-9247-9391
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication7f4a528c-bf0f-4895-ac98-4353fe38c68a
relation.isAuthorOfPublication.latestForDiscovery7f4a528c-bf0f-4895-ac98-4353fe38c68a

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