Publication
Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts
| dc.contributor.author | Encarnação, Marisa | |
| dc.contributor.author | Ribeiro, Isaura | |
| dc.contributor.author | David, Hugo | |
| dc.contributor.author | Coutinho, Maria Francisca | |
| dc.contributor.author | Quelhas, Dulce | |
| dc.contributor.author | Alves, Sandra | |
| dc.date.accessioned | 2024-02-14T10:05:27Z | |
| dc.date.available | 2024-02-14T10:05:27Z | |
| dc.date.issued | 2023-10-25 | |
| dc.description | (This article belongs to the Section Genetic Diagnosis) | |
| dc.description.abstract | Niemann-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.sponsorship | This research was funded by national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project EXPL/BTM-TEC/1477/2021. This work was also financially supported with funding from FCT/MCTES (UIDB/00211/2020) through national funds. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Genes (Basel). 2023 Oct 25;14(11):1990. doi: 10.3390/genes14111990. Review | |
| dc.identifier.doi | 10.3390/genes14111990 | pt_PT |
| dc.identifier.issn | 2073-4425 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/9099 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.relation | RNA-Seq based methods to identify novel disease biomarkers in neurodegenerative metabolic diseases | |
| dc.relation | Center for the Study of Animal Science | |
| dc.relation.publisherversion | https://www.mdpi.com/2073-4425/14/11/1990 | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
| dc.subject | NPC1 Gene | pt_PT |
| dc.subject | Niemann–Pick type C | pt_PT |
| dc.subject | Leaky Variants | pt_PT |
| dc.subject | Molecular Diagnosis | pt_PT |
| dc.subject | Splicing Variants | pt_PT |
| dc.subject | Niemann Pick tipo C | pt_PT |
| dc.subject | Doenças Lisossomais de Sobrecarga | pt_PT |
| dc.subject | Doenças Genéticas | pt_PT |
| dc.subject | Genética Humana | pt_PT |
| dc.title | Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | RNA-Seq based methods to identify novel disease biomarkers in neurodegenerative metabolic diseases | |
| oaire.awardTitle | Center for the Study of Animal Science | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/Concurso de Projetos de Investigação de Caráter Exploratório (PeX) em Todos os Domínios Científicos/EXPL%2FBTM-TEC%2F1477%2F2021/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00211%2F2020/PT | |
| oaire.citation.issue | 11 | pt_PT |
| oaire.citation.title | Genes | pt_PT |
| oaire.citation.volume | 14 | pt_PT |
| oaire.fundingStream | Concurso de Projetos de Investigação de Caráter Exploratório (PeX) em Todos os Domínios Científicos | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.embargofct | Acesso de acordo com política editorial da revista. | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isProjectOfPublication | 88e7e17f-1ff1-4024-b104-311c6dead773 | |
| relation.isProjectOfPublication | 69b75eb9-6f25-4ad8-98db-6cc7e9bcdcc7 | |
| relation.isProjectOfPublication.latestForDiscovery | 69b75eb9-6f25-4ad8-98db-6cc7e9bcdcc7 |