Dominant non-coding repeat expansions in human disease

Genome Dynamics
K A DickLaura P W Ranum

Abstract

The general model that dominant diseases are caused by mutations that result in a gain or change in function of the corresponding protein was challenged by the discovery that the myotonic dystrophy type 1 mutation is a CTG expansion located in the 3' untranslated portion of a kinase gene. The subsequent discovery that a similar transcribed but untranslated CCTG expansion in an intron causes the same multisystemic features in myotonic dystrophy type 2 (DM2), along with other developments in the DM1 field, demonstrate a mechanism in which these expansion mutations cause disease through a gain of function mechanism triggered by the accumulation of transcripts containing CUG or CCUG repeat expansions. A similar RNA gain of function mechanism has also been implicated in fragile X tremor ataxia syndrome (FXTAS) and may play a role in pathogenesis of other non-coding repeat expansion diseases, including spinocerebellar ataxia type 8 (SCA8), SCA10, SCA12 and Huntington disease-like 2.

Citations

Sep 4, 2009·Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society·Henry L Paulson
May 9, 2012·Expert Opinion on Drug Discovery·Deeksha BhartiyaVinod Scaria
Oct 7, 2009·Acta Neurologica Scandinavica·V Rakocevic StojanovicS Apostolski
Jun 23, 2009·The Journal of Pathology·Reiner A Veitia
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Jan 18, 2011·Journal of Molecular Biology·Anna L LudwigPaul J Hagerman

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