Wegner M (2004)
Publication Type: Journal article, Original article
Publication year: 2004
Publisher: Nature Publishing Group
Pages Range: 361-369
Journal Issue: 36
DOI: 10.1038/ng1322
The molecular mechanisms by which different mutations in the same gene can result in distinct disease phenotypes remain largely unknown. Truncating mutations of SOX10 cause either a complex neurocristopathy designated PCWH or a more restricted phenotype known as Waardenburg-Shah syndrome (WS4; OMIM 277580). Here we report that although all nonsense and frameshift mutations that cause premature termination of translation generate truncated SOX10 proteins with potent dominant-negative activity, the more severe disease phenotype, PCWH, is realized only when the mutant mRNAs escape the nonsense-mediated decay (NMD) pathway. We observe similar results for truncating mutations of MPZ that convey distinct myelinopathies. Our experiments show that triggering NMD and escaping NMD may cause distinct neurological phenotypes.
APA:
Wegner, M. (2004). Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations. Nature Genetics, 36, 361-369. https://doi.org/10.1038/ng1322
MLA:
Wegner, Michael. "Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations." Nature Genetics 36 (2004): 361-369.
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