The diagnosis of inherited neurological and neuromuscular disorders relies on clinical features, natural history, and the mode of inheritance. Complex factors, however, often obscure the familial tendency of these diseases and many patients go undiagnosed or are confused with noninherited disorders. Histopathologic, imaging, and electrophysiologic testing help in the identification, understanding, and characterization, but this testing is often inadequate. Molecular biology has provided for major advances in the understanding and diagnosis of these disorders. The Human Genome Project has allowed for rapid advancements in cytogenetics and other DNA testing, as both the normal and pathologic processes have been mapped, cloned, and characterized. Such work has led to specific testing and improved care of patients and their families. The types of DNA mutation implicated include trinucleotide repeat expansions, point mutations, insertions, deletions, and duplications. This chapter describes selected disorders that exemplify the types of mutation and molecular mechanism involved in neurological and neuromuscu-lar disorders. Because molecular testing without consideration of clinical features and mode of inheritance is inadequate, a brief clinical description of these selected disorders is also provided.
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