Myotonic dystrophy--a multigene disorder.
Myotonic dystrophy (DM1) is the most common form of adult muscular dystrophy with an estimated incidence of 1/8000 births. The mutation responsible for this condition is an expanded CTG repeat within the 3' untranslated region of the protein kinase gene DMPK. Strong nucleosome positioning signals created by this expanded repeat cause a reduction in gene expression within the region. This "field effect" is further confounded by the retention of DMPK expansion containing transcripts, which acquire a toxic gain of function. Thus, the various manifestations exhibited by DM1 patients can be explained as a result of gene silencing, nuclear retention and sequestration of nuclear factors by the CUG containing transcript.
Larkin
K
K
Department of Genetics, Queens Medical Centre, University of Nottingham, Nottingham, UK.
Fardaei
M
M
D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D009223:Myotonic Dystrophy / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D018911:Trinucleotide Repeats
C585517:DMPK protein, human; D018398:Homeodomain Proteins; C106687:SIX5 protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases