Autosomal dominant polycystic kidney disease, the most common monogenetic disorder, is
characterized by gradual replacement of normal renal parenchyma by fluid-filled cysts.
Mutations in either PKD1 or PKD2 cause autosomal dominant polycystic kidney disease.
Pkd1−/− or Pkd2−/− mice develop rapid renal cystic disease and exhibit embryonic lethality;
this supports the “two-hit” hypothesis, which proposes that a germline mutation in PKD1 (or
PKD2) followed by a second somatic mutation later in life is responsible for the phenotype …