Autosomal dominant polycystic kidney disease: modification of disease progression.
Autosomal dominant polycystic kidney disease is a common inherited disorder, which is characterised by the formation of fluid-filled cysts in both kidneys that leads to progressive renal failure. Mutations in two genes, PKD1 and PKD2, are associated with the disorder. We describe the various factors that cause variation in disease progression between patients. These include whether the patient has a germline mutation in the PKD1 or in the PKD2 gene, and the nature of the mutation. Detection of mutations in PKD1 is complicated, but the total number identified is rising and will enable genotype-to-phenotype studies. Another factor affecting disease progression is the occurrence of somatic mutations in PKD genes. Furthermore, modifying genes might directly affect the function of polycystins by affecting the rate of somatic mutations or the rate of protein interactions, or they might affect cystogenesis itself or clinical factors associated with disease progression. Finally, environmental factors that speed up or slow down progress towards chronic renal failure have been identified in rodents.
Peters
D J
DJ
Department of Human and Clinical Genetics, Leiden University Medical Centre, 2333AL, Leiden, Netherlands. d.j.m.peters@lumc.nl
Breuning
M H
MH
D000818:Animals; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics*; D050396:TRPP Cation Channels
D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels