The muscular dystrophies mentioned above were the first human diseases shown to be caused by mutations in voltage-gated ion channels. Nearly two dozen rare diseases of brain and heart are now known to have a similar basis in ion channel mutations. These discoveries are leading toward new insights into the function and malfunction of these membrane proteins in excitable membranes in muscle cells and neurons. Many other rare, monogenic, and episodic neurologic disorders are recognized. To understand the pathophysiologic basis of these diseases, we are attempting to map and clone some of the genes causing these disorders.
Studies are under way to determine the role of the encoded protein.
Efforts are under way to clone and characterize these genes. Complex Disorders Identifying genes that cause complex, polygenic disorders such as epilepsy and migraine, which share many features with the channelopathies described here, is much more difficult. Subtle electrophysiological abnormalities result from the ion channel mutants mentioned above. Although not disease causing alone, such variations in neurons may lead to an increased or decreased predisposition or risk of seizures, for example. In this model, variations in a number of different genes will usually cancel one another out.