CNS DEGENERATION IN MYOTONIC DYSTROPHY TYPES 1 AND 2

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To better define the pathophysiological basis of myotonic dystrophy (DM), we will clarify the differences and similarities of central nervous system (CNS) involvement in DM1 (chromosome 19) and DM2 (chromosome 3), an approach we successfully used to clarify the role of RNA in many other features of this multisystemic disease. Using the unique patient populations at the University of Minnesota, we will study 40 true adult-onset DM1 subjects, 40 DM2 adults, 40 controls, and 40 adults with congenital DM1, comparing neuropsychological and volumetric MRI, with diffusion tensor imaging and fractional anisotropy used to determine gray and white matter pathology. This will allow us to identify unusual pathological similarities in the two diseases, which are likely to be caused by the RNA effect. In all of these subjects, as well as in a larger group of DM1 and DM2 subjects we will determine whether the degree of splicing change in relevant genes (insulin receptor, chloride channel, myotubularin) correlates with repeat length or methylation of DM1 locus. These results will help determine the pathyophysiological effects of DM on the CNS and the role of RNA repeat expansions and methylation in creating those features of the disease.