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)
Showing the most recent 10 out of 535 publications