Myotonic dystrophy - A multigene disorder

Myotonic dystrophy (DMI) is the most common form of adult muscular dystroph y with an estimated incidence of 1/8000 births. The mutation responsible fo r this condition is an expanded CTG repeat within the 3' untranslated regio n of the protein kinase gene DMPK. Strong nucleosome positioning signals cr eated by this expanded repeat cause a reduction in gene expression within t he region. This "field effect" is further confounded by the retention of DM PK expansion containing transcripts, which acquire a toxic gain of function . Thus, the various manifestations exhibited by DM1 patients can be explain ed as a result of gene silencing, nuclear retention and sequestration of nu clear factors by the CUG containing transcript. (C) 2001 Elsevier Science I nc.