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Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts

2023-10Journal article Open access
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dc.contributor.authorEncarnação, Marisa
dc.contributor.authorRibeiro, Isaura
dc.contributor.authorDavid, Hugo
dc.contributor.authorCoutinho, Maria Francisca
dc.contributor.authorQuelhas, D
dc.contributor.authorAlves, Sandra
dc.date.accessioned2024-07-23T10:29:01Z
dc.date.available2024-07-23T10:29:01Z
dc.date.issued2023-10
dc.description.abstractNiemann-Pick type C (NPC, ORPHA: 646) is a neuro-visceral, psychiatric disease caused predominantly by pathogenic variants in the NPC1 gene or seldom in NPC2. The rarity of the disease, and its wide range of clinical phenotypes and ages of onset, turn the diagnosis into a significant challenge. Other than the detailed clinical history, the typical diagnostic work-up for NPC includes the quantification of pathognomonic metabolites. However, the molecular basis diagnosis is still of utmost importance to fully characterize the disorder. Here, the authors provide an overview of splicing variants in the NPC1 and NPC2 genes and propose a new workflow for NPC diagnosis. Splicing variants cover a significant part of the disease-causing variants in NPC. The authors used cDNA analysis to study the impact of such variants, including the collection of data to classify them as leaky or non-leaky pathogenic variants. However, the presence of naturally occurring spliced transcripts can misdiagnose or mask a pathogenic variant and make the analysis even more difficult. Analysis of the NPC1 cDNA in NPC patients in parallel with controls is vital to assess and detect alternatively spliced forms. Moreover, nonsense-mediated mRNA decay (NMD) analysis plays an essential role in evaluating the naturally occurring transcripts during cDNA analysis and distinguishing them from other pathogenic variants' associated transcripts.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEncarnação M, Ribeiro I, David H, Coutinho MF, Quelhas D, Alves S. Challenges in the Definitive Diagnosis of Niemann-Pick Type C-Leaky Variants and Alternative Transcripts. Genes (Basel). 2023;14(11):1990. doi:10.3390/genes14111990pt_PT
dc.identifier.doi10.3390/genes14111990pt_PT
dc.identifier.issn2073-4425
dc.identifier.urihttp://hdl.handle.net/10400.16/3017
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationEXPL/BTM-TEC/1477/2021pt_PT
dc.relationCenter for the Study of Animal Science
dc.relation.publisherversionhttps://doi.org/10.3390/genes14111990pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectNPC1 genept_PT
dc.subjectNiemann–Pick type Cpt_PT
dc.subjectLeaky variantspt_PT
dc.subjectmolecular diagnosispt_PT
dc.subjectsplicing variantspt_PT
dc.titleChallenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcriptspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCenter for the Study of Animal Science
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00211%2F2020/PT
oaire.citation.conferencePlaceSwitzerlandpt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage1990pt_PT
oaire.citation.titleGenespt_PT
oaire.citation.volume14pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameRibeiro
person.familyNameQuelhas
person.givenNameIsaura
person.givenNameDulce
person.identifier.ciencia-id321C-808C-F78D
person.identifier.ciencia-id921C-8052-6FC5
person.identifier.orcid0000-0003-1067-8248
person.identifier.orcid0000-0001-9989-9236
person.identifier.scopus-author-id7003759504
person.identifier.scopus-author-id6507796178
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication29e0aeb0-d909-44c4-9b02-76c4718000fd
relation.isAuthorOfPublicationa7117e6e-c216-451e-9f9a-b2cd8dab81e4
relation.isAuthorOfPublication.latestForDiscoverya7117e6e-c216-451e-9f9a-b2cd8dab81e4
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