Repository logo
 
Publication

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

2020-09-01Journal article Open access
Simple item page
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.accessioned2021-03-13T11:16:26Z
dc.date.available2021-03-13T11:16:26Z
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.sponsorshipThis research was partially supported by NORTE2020 (NORTE-01-0246-FEDER-000014 DESVENDAR “DEScobrir, VENcer as Doenças Raras”, FCT (Fundação para a Ciência e a Tecnologia—MCTES, Portugal): project PTDC/BBB-BMD/6301/2014 and UIDB/00211/2020.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Mol Sci. 2020 Sep 1;21(17):6355. doi: 10.3390/ijms21176355pt_PT
dc.identifier.doi10.3390/ijms21176355pt_PT
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10400.18/7437
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationCenter for the Study of Animal Science
dc.relation.publisherversionhttps://www.mdpi.com/1422-0067/21/17/6355pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectLysosomal Storage Disorderspt_PT
dc.subjectCLN7pt_PT
dc.subjectGM2 Gangliosidosispt_PT
dc.subjectGM2A Genept_PT
dc.subjectBioinformatics Analysispt_PT
dc.subjectDiagnostics Odysseypt_PT
dc.subjectMolecular Genetic Testingpt_PT
dc.subjectNext-generation Sequencingpt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectGenómicapt_PT
dc.subjectDoenças Lisossomais de Sobrecargapt_PT
dc.titleAssessing Lysosomal Disorders in the NGS Era: Identification of Novel Rare Variantspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCenter for the Study of Animal Science
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBBB-BMD%2F6301%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00211%2F2020/PT
oaire.citation.issue17pt_PT
oaire.citation.startPage6355pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume21pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication82ca1b56-9fd8-4a11-b89d-6bc8dd3c27f1
relation.isProjectOfPublication69b75eb9-6f25-4ad8-98db-6cc7e9bcdcc7
relation.isProjectOfPublication.latestForDiscovery82ca1b56-9fd8-4a11-b89d-6bc8dd3c27f1

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
ijms-21-06355.pdf
Size:
3.97 MB
Format:
Adobe Portable Document Format
Download

Collections

DGH - Artigos em revistas internacionais