Genetics and molecular pathogenesis of the myotonic dystrophies.
Pathogenic repeat expansions were initially identified as causing either a loss of gene product, such as in fragile X mental retardation, or an expansion of a polyglutamine region of a protein, as was first shown in spinobulbar muscular atrophy (Kennedy's disease). The pathogenic effect of the repeat expansion in myotonic dystrophy type 1, however, has been controversial because it does not encode a protein but nonetheless results in a highly penetrant dominant disease. Clinical and molecular characterization of myotonic dystrophy types 1 and 2 have now demonstrated a novel disease mechanism involving pathogenic effects of repeat expansions that are expressed in RNA but are not translated into protein.
Day
John W
JW
Department of Neurology, Institute of Human Genetics, MMC 206, University of Minnesota School of Medicine, 420 Delaware Street SE, Minneapolis, MN 55455, USA. johnday@umn.edu
Ranum
Laura P W
LP
D042622:DNA Repeat Expansion; D006801:Humans; D009223:Myotonic Dystrophy / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology