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DC Field | Value | Language |
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dc.contributor.author | Bolze, Alexandre | - |
dc.contributor.author | Abhyankar, Avinas | - |
dc.contributor.author | Grant, Audrey V. | - |
dc.contributor.author | Patel, Bhavi | - |
dc.contributor.author | Yadav, Ruchi | - |
dc.contributor.author | Byun, Minji | - |
dc.contributor.author | Caillez, Daniel | - |
dc.contributor.author | Emile, Jean-François | - |
dc.contributor.author | Pastor Anglada, Marçal | - |
dc.contributor.author | Abel, Laurent | - |
dc.contributor.author | Puel, Anne | - |
dc.contributor.author | Govindarajan, Rajgopal | - |
dc.contributor.author | Pontual, Loic de | - |
dc.contributor.author | Casanova, Jean-Laurent | - |
dc.date.accessioned | 2013-05-07T11:19:52Z | - |
dc.date.available | 2013-05-07T11:19:52Z | - |
dc.date.issued | 2012-01 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2445/43148 | - |
dc.description.abstract | We investigated two siblings with granulomatous histiocytosis prominent in the nasal area, mimicking rhinoscleroma and Rosai-Dorfman syndrome. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous frameshift deletion in SLC29A3, which encodes human equilibrative nucleoside transporter-3 (hENT3). Germline mutations in SLC29A3 have been reported in rare patients with a wide range of overlapping clinical features and inherited disorders including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, and Faisalabad histiocytosis. With the exception of insulin-dependent diabetes and mild finger and toe contractures in one sibling, the two patients with nasal granulomatous histiocytosis studied here displayed none of the many SLC29A3-associated phenotypes. This mild clinical phenotype probably results from a remarkable genetic mechanism. The SLC29A3 frameshift deletion prevents the expression of the normally coding transcripts. It instead leads to the translation, expression, and function of an otherwise noncoding, out-of-frame mRNA splice variant lacking exon 3 that is eliminated by nonsense-mediated mRNA decay (NMD) in healthy individuals. The mutated isoform differs from the wild-type hENT3 by the modification of 20 residues in exon 2 and the removal of another 28 amino acids in exon 3, which include the second transmembrane domain. As a result, this new isoform displays some functional activity. This mechanism probably accounts for the narrow and mild clinical phenotype of the patients. This study highlights the"rescue" role played by a normally noncoding mRNA splice variant of SLC29A3, uncovering a new mechanism by which frameshift mutations can be hypomorphic. | - |
dc.format.extent | 11 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Public Library of Science (PLoS) | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0029708 | - |
dc.relation.ispartof | PLoS One, 2012, vol. 7, num. 1, p. e29708 | - |
dc.relation.uri | http://dx.doi.org/10.1371/journal.pone.0029708 | - |
dc.rights | cc-by (c) Bolze, A. et al., 2012 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) | - |
dc.subject.classification | Genètica | - |
dc.subject.classification | Fenotip | - |
dc.subject.classification | RNA | - |
dc.subject.other | Genetics | - |
dc.subject.other | Phenotype | - |
dc.subject.other | RNA | - |
dc.title | A mild form of SLC29A3 disorder: a frameshift deletion leads to the paradoxical translation of an otherwise noncoding mRNA splice variant | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 609742 | - |
dc.date.updated | 2013-05-07T11:19:52Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 22238637 | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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609742.pdf | 3.4 MB | Adobe PDF | View/Open |
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