Myotonic Dystrophies: An Overview

This chapter discusses the disease-causing mechanisms of myotonic dystrophies (DM), which constitutes a group of disorders characterized by myotonia, weakness, and atrophy of the muscle, and is associated with variable multisystemic phenotypes. Till date, two genetic mutations have been identified, including the (CTG)_n repeat expansion in myotonic dystrophy type 1 (DM1) and the (CCTG)_n repeat expansion in DM2. These repeats are located in a noncoding region of the respective genes, DMPK and ZNF9. The currently available evidence suggests that a transdominant gain of function by the mutant RNA transcripts containing expanded repeats plays a central role in the pathogenic mechanism. Experimental models of these repeats have provided valuable insights into the molecular mechanism of the repeat instability observed in patients with these diseases. Technological developments in researches, such as DNA testing offer accurate diagnosis of DM1 and DM2. For DM1, polymerase chain reaction (PCR) across the repeat region can identify normal individuals by detecting two (CTG)_n alleles in the normal repeat range, whereas for DM2 patients an additional DM2 repeat assay (RA) that consists of amplifying the CCTG repeat by repeat-primed PCR and probing the resultant product with an internal probe is recommended.