STUDY OF INHERITED NEUROLOGICAL DISEASES

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。 一些神经系统疾病的诊断通常需要组织活检。肌肉和皮肤这两个相对容易获取的组织，为了临床目的，通常会进行安全的活组织检查。这种临床指示的活组织检查通常是在神经肌肉疾病的情况下进行的，但情况并不总是如此；例如，肌肉活组织检查是为了确认线粒体脑病(在这种情况下可以看到粗糙的红色纤维)，皮肤活组织检查是为了诊断CADASIL。在研究背景下，肌肉和皮肤活检为研究提供了独特的资源，如下所述。 与遗传性神经肌肉疾病有关的基因通常只在肌肉中表达。在许多遗传性疾病中，没有替代的疾病模型系统可供研究。相反，在一些存在动物模型的疾病中，它们不足以检验与患者特定基因突变相关的假说。Duchenne肌营养不良症(DMD)就是一个例子。MDX小鼠被认为是DMD的标准模型，因为在dystrophin基因的外显子23中存在过早的终止密码子突变。然而，人类疾病是由多种dystrophin突变引起的，并与dystrophin蛋白水平和dystrophin Alternate mRNA转录本的广泛差异有关。肌营养不良蛋白的mRNA和蛋白的特征需要肌肉活检。 该方案旨在补充其他两个现行方案：营养不良转化性研究(GCRC03-32；IRB#10966)和遗传性神经疾病的分子特征(GCRC04-07；IRB6697)。在每个项目中，对来自受试者淋巴细胞样本的基因组DNA的研究都导致了关于分子机制的假设，这些假设只有通过进一步的组织特异性基因转录或剪接或蛋白质表达的研究才能得到检验。 这项研究的目的是： 为新的或罕见的神经和神经肌肉综合征的分子特征提供必要的生物材料，包括： A.用于RNA、DNA和蛋白质分析的组织 用于实验目的的培养细胞系(成肌细胞和成纤维细胞)

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. The diagnosis of some neurologic diseases often requires tissue biopsy. Two relatively easily accessible tissues, muscle and skin, are routinely and safely biopsied for clinical purposes. Such clinically-indicated biopsies are usually performed in the setting of neuromuscular disease, but this is not always the case; as examples, muscle biopsies are performed for the confirmation of mitochondrial encephalopathy (in which ragged-red fibers may be seen), and skin biopsies for the diagnosis of CADASIL. In the research setting, muscle and skin biopsies provide unique resources for study, as discussed below. Genes involved in inherited neuromuscular disorders are often expressed only in muscle. In many inherited diseases, no alternate model systems of disease exist for study. Conversely, in some diseases where animal models exist, they are inadequate for the testing of hypotheses related to patient-specific gene mutations. One example of this is found in Duchenne Muscular Dystrophy (DMD). The mdx mouse is accepted as a standard model of DMD, due to the presence of a premature stop codon mutation within exon 23 of the dystrophin gene. However, the human disease is due to a wide variety of dystrophin mutations, and is associated with wide variation in dystrophin protein levels and in dystrophin alternate mRNA transcripts. Characterization of dystrophin mRNA and protein requires muscle biopsy. This protocol is designed to complement two other current protocols: Translational Research in the Dystrophinopathies (GCRC03-32; IRB#10966) and Molecular Characterization of Inherited Neurologic Disease (GCRC 04-07; IRB#6697). In each of these projects, studies of genomic DNA derived from subject lymphocyte samples has led to hypotheses regarding molecular mechanisms that may be tested only by further studies of tissue-specific gene transcription or splicing, or protein expression The objective of this study is: To provide biological materials necessary for the molecular characterization of novel or rare neurological and neuromuscular syndromes, including: a. Tissues for RNA, DNA, and protein analysis b. Cultured cell lines for experimental purposes (myoblasts and fibroblasts)