“Mistakes Happen”: Somatic Mutation and Disease

An intriguing quality of many genetic diseases in humans is the significant intrafamilial variability observed in their clinical presentation. It seems to be likely that definition of the factors responsible for such differences will provide important clues to the normal function of the genes and to the pathobiology of their associated diseases. For some diseases, such as fragile X syndrome and Huntington disease, it has been shown that genetically related individuals do not necessarily have identical germ-line mutations, and instability at the mutant loci may account for much of the observed clinical variation.