Myotonic dystrophy: clinical and molecular parallels between myotonic dystrophy type 1 and type 2.
Myotonic dystrophy (DM) is a dominantly inherited disorder with a peculiar pattern of multisystemic clinical features affecting skeletal muscle, the heart, the eye, and the endocrine system. Two genetic loci have been associated with the DM phenotype: DM1 on chromosome 19, and DM2 on chromosome 3. In 1992, the mutation responsible for DM1 was identified as a CTG expansion located in the 3' untranslated region of the dystrophica myotonica-protein kinase gene (DMPK). How this untranslated CTG expansion causes DM1 has been a matter of controversy. The recent discovery that DM2 is caused by an untranslated CCTG expansion, along with other discoveries on DM1 pathogenesis, indicate that the clinical features common to both diseases are caused by a gain of function RNA mechanism in which the CUG and CCUG repeats alter cellular function, including alternative splicing of various genes.
Ranum
Laura P W
LP
Institute of Human Genetics, University of Minnesota, MMC 206, 420 Delaware Street SE, Minneapolis, MN 55455, USA. ranum001@umn.edu
Day
John W
JW
D000818:Animals; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D009154:Mutation; D020967:Myotonic Disorders / Q000235:genetics / Q000473:pathology; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000473:pathology; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
C433227:CNBP protein, human; C585517:DMPK protein, human; D018398:Homeodomain Proteins; D016601:RNA-Binding Proteins; C106687:SIX5 protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases