title: Dominant non-coding repeat expansions in human disease.
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.
authors: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minn., USA.
authors: K A
authors: KA
authors: Dick
authors: J M
authors: JM
authors: Margolis
authors: J W
authors: JW
authors: Day
authors: L P W
authors: LPW
authors: Ranum
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D004247:DNA; D042622:DNA Repeat Expansion; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D005821:Genetic Techniques; D006801:Humans; D051379:Mice; D018895:Microsatellite Repeats; D008957:Models, Genetic; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics
chemical_list: D004247:DNA