Expanding complexity in myotonic dystrophy.
Myotonic dystrophy (DM) is a highly variable multisystemic disease belonging to the rather special class of trinucleotide expansion disorders. DM results from dynamic expansion of a perfect (CTG)n repeat situated in a gene-dense region on chromosome 19q. Based on findings in patient materials or cellular and animal models, many mechanisms for the causes and consequences of repeat expansion have been proposed; however, none of them has enjoyed prolonged support. There is now circumstantial evidence that long (CTG)n repeats may affect the expression of any of at least three genes, myotonic dystrophy protein kinase (DMPK), DMR-N9 (gene 59), and a DM-associated homeodomain protein (DMAHP). Furthermore, the new findings suggest that DM is not a simple gene-dosage or gain-or-loss-of-function disorder but that entirely new pathological pathways at the DNA, RNA, or protein level may play a role in its manifestation.
Groenen
P
P
Department of Cell Biology and Histology, Medical Faculty, University of Nijmegen, The Netherlands.
Wieringa
B
B
D000818:Animals; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D005314:Embryonic and Fetal Development; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D009223:Myotonic Dystrophy / Q000196:embryology / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D018911:Trinucleotide Repeats
C585517:DMPK protein, human; C081088:DMWD protein, human; D018398:Homeodomain Proteins; D011506:Proteins; C106687:SIX5 protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases