Portal de investigação
NPC1 silent variant induces skipping of exon 11 (p.V562V) and unfolded protein response was found in a specific Niemann-Pick type C patient
Data de publicação:
Data Ahead of Print:
Autores da FMUP
Participantes de fora da FMUP
- Encarnaçao, M
- Coutinho, MF
- Cho, SM
- Ribeiro, I
- Santos, JI
- Quelhas, D
- Lacerda, L
- Teles, EL
- Futerman, AH
- Vilarinho, L
- Alves, S
Unidades de investigação
Abstract
Background: Niemann-Pick type C (NPC, MIM #257220) is a neuro-visceral disease, caused predominantly by pathogenic variants in theNPC1gene. Here we studied patients with clinical diagnosis of NPC but inconclusive results regarding the molecular analysis. Methods: We used a Next-Generation Sequencing (NGS)-panel followed by cDNA analysis. Latter, we used massively parallel single-cell RNA-seq (MARS-Seq) to address gene profiling changes and finally the effect of different variants on the protein and cellular levels. Results: We identified novel variants and cDNA analysis allowed us to establish the functional effect of a silent variant, previously reported as a polymorphism. We demonstrated that this variant induces the skipping of exon 11 leading to a premature stop codon and identified it in NPC patients from two unrelated families. MARS-Seq analysis showed that a number of upregulated genes were related to the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress in one specific patient. Also, for all analyzed variants, the NPC1 protein was partially retained in the ER. Conclusion: We showed that theNPC1silent polymorphism (p.V562V) is a disease-causing variant in NPC and that the UPR is upregulated in an NPC patient.
Dados da publicação
- ISSN/ISSNe:
- 2324-9269, 2324-9269
- Tipo:
- Article
- Páginas:
- -
- DOI:
- 10.1002/mgg3.1451
- Link para outro recurso:
- www.scopus.com
MOLECULAR GENETICS & GENOMIC MEDICINE John Wiley & Sons Inc.
Citações Recebidas na Web of Science: 6
Citações Recebidas na Scopus: 13
Documentos
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Filiações
Keywords
- exon skipping; Niemann-Pick type C; NPC1; RNA-seq; silent variant; unfolded protein response
Campos de estudo
Financiamento
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Citar a publicação
Encarnaçao M,Coutinho MF,Cho SM,Cardoso M,Ribeiro I,Chaves P,Santos JI,Quelhas D,Lacerda L,Teles EL,Futerman AH,Vilarinho L,Alves S. <i>NPC1</i> silent variant induces skipping of exon 11 (p.V562V) and unfolded protein response was found in a specific Niemann-Pick type C patient. Mol. Genetics Genom. Med. 2020. 8. (11):e1451. IF:2,183. (3).
