ABSTRACT
Distinct Mechanisms Downstream of the Repeat Expansion Are Implicated in the Molecular Basis of Myotonic Dystrophy Type 1 K eith Joh n son and Ram i Ja rjo u r
Myotonic dystrophy type 1 (DM1) is the most common inherited muscular dystrophy affecting adults. The underlying mutation is the same in all patients with DM1, namely a trinucleotide (CTG) repeat expansion. There is now conclusive evidence that there are several distinct molecular mechanisms that probably occur concomitandy in the tissues of individuals affected by DM1 leading to the array of symptoms they exhibit. These include chromatin mediated and RNA-processing defects that alter the normal expression pat terns of numerous genes, some of which explain specific symptoms such as myotonia, insulin resistance and cataract that are part of the DM 1 phenotype. A range of animal models have been generated that replicate many of the key molecular and phenotypic features of DM 1.
