Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/42783
Título: | Novel candidate blood-based transcriptional biomarkers of Machado-Joseph disease |
Autor(es): | Raposo, Mafalda Bettencourt, Conceição Maciel, P. Gao, Fuying Ramos, Amanda Kazachkova, Nadiya Vasconcelos, João Kay, Teresa Rodrigues, Ana João Bettencourt, Bruno Bruges-Armas, Jácome Geschwind, Daniel Coppola, Giovanni Lima, Manuela |
Palavras-chave: | Spinocerebellar ataxia type 3 Polyglutamine disease Gene expression Ataxin-3 Microarray |
Data: | 2015 |
Editora: | Wiley |
Revista: | Movement Disorders |
Resumo(s): | BACKGROUND: Machado-Joseph disease (or spinocerebellar ataxia type 3) is a late-onset polyglutamine neurodegenerative disorder caused by a mutation in the ATXN3 gene, which encodes for the ubiquitously expressed protein ataxin-3. Previous studies on cell and animal models have suggested that mutated ataxin-3 is involved in transcriptional dysregulation. Starting with a whole-transcriptome profiling of peripheral blood samples from patients and controls, we aimed to confirm abnormal expression profiles in Machado-Joseph disease and to identify promising up-regulated genes as potential candidate biomarkers of disease status. METHODS: The Illumina Human V4-HT12 array was used to measure transcriptome-wide gene expression in peripheral blood samples from 12 patients and 12 controls. Technical validation and validation in an independent set of samples were performed by quantitative real-time polymerase chain reaction (PCR). RESULTS: Based on the results from the microarray, twenty six genes, found to be up-regulated in patients, were selected for technical validation by quantitative real-time PCR (validation rate of 81% for the up-regulation trend). Fourteen of these were further tested in an independent set of 42 patients and 35 controls; 10 genes maintained the up-regulation trend (FCGR3B, CSR2RA, CLC, TNFSF14, SLA, P2RY13, FPR2, SELPLG, YIPF6, and GPR96); FCGR3B, P2RY13, and SELPLG were significantly up-regulated in patients when compared with controls. CONCLUSIONS: Our findings support the hypothesis that mutated ataxin-3 is associated with transcription dysregulation, detectable in peripheral blood cells. Furthermore, this is the first report suggesting a pool of up-regulated genes in Machado-Joseph disease that may have the potential to be used for fine phenotyping of this disease. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/42783 |
DOI: | 10.1002/mds.26238 |
ISSN: | 0885-3185 |
Versão da editora: | http://onlinelibrary.wiley.com |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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mds26238.pdf | 325,12 kB | Adobe PDF | Ver/Abrir |