Increased transcript diversity: novel splicing variants of Machado–Joseph Disease gene (ATXN3) View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2010-05

AUTHORS

Conceição Bettencourt, Cristina Santos, Rafael Montiel, Maria do Carmo Costa, Pablo Cruz-Morales, Liliana Ribeiro Santos, Nelson Simões, Teresa Kay, João Vasconcelos, Patrícia Maciel, Manuela Lima

ABSTRACT

Machado-Joseph disease (MJD) is a late-onset neurodegenerative disorder that presents clinical heterogeneity not completely explained by its causative mutation. MJD is caused by an expansion of a CAG tract at exon 10 of the ATXN3 gene (14q32.1), which encodes for ataxin-3. The main goal of this study was to analyze the occurrence of alternative splicing at the ATXN3 gene, by sequencing a total of 415 cDNAs clones (from 20 MJD patients and 14 controls). Two novel exons are described for the ATXN3 gene. Fifty-six alternative splicing variants, generated by four types of splicing events, were observed. From those variants, 50 were not previously described, and 26 were only found in MJD patients samples. Most of the variants (85.7%) present frameshift, which leads to the appearance of premature stop codons. Thirty-seven of the observed variants constitute good targets to nonsense-mediated decay, the remaining are likely to be translated into at least 20 different isoforms. The presence of ataxin-3 domains was assessed, and consequences of domain disruption are discussed. The present study demonstrates high variability in the ATXN3 gene transcripts, providing a basis for further investigation on the contribution of alternative splicing to the MJD pathogenic process, as well as to the larger group of the polyglutamine disorders. More... »

PAGES

193-202

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10048-009-0216-y

DOI

http://dx.doi.org/10.1007/s10048-009-0216-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012388368

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19714377


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