Autosomal dominant polycystic kidney disease: a two-hit model.

The clinical and histopathologic variability of this common genetic disorder-a leading cause of renal failure-cannot be explained by inherited mutation. Instead, the disease evidently progresses by a second hit: somatic mutation superimposed on germline mutation. The source of the mutability appears to be DNA triple-helixing, as mediated by some odd genetic code, the longest polypyrimidine tract ever found in the human genome.