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

Detalhes bibliográficos
Autor(a) principal: Encarnação, Marisa
Data de Publicação: 2023
Outros Autores: Ribeiro, Isaura, David, Hugo, Coutinho, Maria Francisca, Quelhas, Dulce, Alves, Sandra
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/9099
Resumo: (This article belongs to the Section Genetic Diagnosis)
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spelling Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative TranscriptsNPC1 GeneNiemann–Pick type CLeaky VariantsMolecular DiagnosisSplicing VariantsNiemann Pick tipo CDoenças Lisossomais de SobrecargaDoenças GenéticasGenética Humana(This article belongs to the Section Genetic Diagnosis)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.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.Repositório Científico do Instituto Nacional de SaúdeEncarnação, MarisaRibeiro, IsauraDavid, HugoCoutinho, Maria FranciscaQuelhas, DulceAlves, Sandra2024-02-14T10:05:27Z2023-10-252023-10-25T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/9099engGenes (Basel). 2023 Oct 25;14(11):1990. doi: 10.3390/genes14111990. Review2073-442510.3390/genes14111990info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-17T01:31:12Zoai:repositorio.insa.pt:10400.18/9099Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:38:33.672257Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts
title Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts
spellingShingle Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts
Encarnação, Marisa
NPC1 Gene
Niemann–Pick type C
Leaky Variants
Molecular Diagnosis
Splicing Variants
Niemann Pick tipo C
Doenças Lisossomais de Sobrecarga
Doenças Genéticas
Genética Humana
title_short Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts
title_full Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts
title_fullStr Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts
title_full_unstemmed Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts
title_sort Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts
author Encarnação, Marisa
author_facet Encarnação, Marisa
Ribeiro, Isaura
David, Hugo
Coutinho, Maria Francisca
Quelhas, Dulce
Alves, Sandra
author_role author
author2 Ribeiro, Isaura
David, Hugo
Coutinho, Maria Francisca
Quelhas, Dulce
Alves, Sandra
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Encarnação, Marisa
Ribeiro, Isaura
David, Hugo
Coutinho, Maria Francisca
Quelhas, Dulce
Alves, Sandra
dc.subject.por.fl_str_mv NPC1 Gene
Niemann–Pick type C
Leaky Variants
Molecular Diagnosis
Splicing Variants
Niemann Pick tipo C
Doenças Lisossomais de Sobrecarga
Doenças Genéticas
Genética Humana
topic NPC1 Gene
Niemann–Pick type C
Leaky Variants
Molecular Diagnosis
Splicing Variants
Niemann Pick tipo C
Doenças Lisossomais de Sobrecarga
Doenças Genéticas
Genética Humana
description (This article belongs to the Section Genetic Diagnosis)
publishDate 2023
dc.date.none.fl_str_mv 2023-10-25
2023-10-25T00:00:00Z
2024-02-14T10:05:27Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/9099
url http://hdl.handle.net/10400.18/9099
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Genes (Basel). 2023 Oct 25;14(11):1990. doi: 10.3390/genes14111990. Review
2073-4425
10.3390/genes14111990
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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