CNS DEGENERATION IN MYOTONIC DYSTROPHY TYPES 1 AND 2

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 为了更好地确定强直性肌营养不良症(DM)的病理生理学基础，我们将阐明中枢神经系统(CNS)参与DM1(19号染色体)和DM2(3号染色体)的异同，我们成功地使用这种方法来阐明RNA在这种多系统疾病的许多其他特征中的作用。利用明尼苏达大学独特的患者群体，我们将研究40名真正的成人发病的DM1受试者、40名DM2成年人、40名对照和40名患有先天性DM1的成年人，比较神经心理学和体积MRI，并使用扩散张量成像和分数各向异性来确定灰质和白质病理。这将使我们能够识别这两种疾病中不寻常的病理相似之处，这很可能是由RNA效应引起的。在所有这些受试者中，以及更多的DM1和DM2受试者中，我们将确定相关基因(胰岛素受体、氯通道、肌管蛋白)的剪接变化程度是否与DM1基因的重复长度或甲基化有关。这些结果将有助于确定糖尿病对中枢神经系统的病理生理影响，以及RNA重复扩增和甲基化在创造这种疾病特征中的作用。

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.