Dominantly inherited, non-coding microsatellite expansion disorders.
Dominantly inherited diseases are generally caused by mutations resulting in gain of function protein alterations. However, a CTG expansion located in the 3' untranslated portion of a kinase gene was found to cause myotonic dystrophy type 1, a multisystemic dominantly inherited disorder. The recent discovery that an untranslated CCTG expansion causes the same constellation of clinical features in myotonic dystrophy type 2 (DM2), along with other recent discoveries on DM1 pathogenesis, have led to the understanding that both DM1 and DM2 mutations are pathogenic at the RNA level. These findings indicate the existence of a new category of disease wherein repeat expansions in RNA alter cellular function. Pathogenic repeat expansions in RNA may also be involved in spinocerebellar ataxia types 8, 10 and 12, and Huntington's disease-like type 2.
Ranum
Laura P W
LP
Institute of Human Genetics, University of Minnesota, MMC 206, 420 Delaware Street SE, Minneapolis, Minnesota 55455, USA. ranum001@umn.edu
Day
John W
JW
D005799:Genes, Dominant; D030342:Genetic Diseases, Inborn; D006801:Humans; D006816:Huntington Disease / Q000235:genetics; D018895:Microsatellite Repeats; D009223:Myotonic Dystrophy / Q000209:etiology / Q000235:genetics; D010641:Phenotype; D012313:RNA; D020754:Spinocerebellar Ataxias / Q000209:etiology / Q000235:genetics; D019680:Trinucleotide Repeat Expansion
D012313:RNA