Autosomal Dominant Polycystic Kidney: Genetics
Section Editor: Dharam M. Ramnani, MD
Virginia Urology, Richmond, VA, USA
Image Description
Genetics: Autosomal dominant polycystic kidney disease (ADPKD) is inherited as an autosomal dominant disorder with complete penetrance (by age 80 years). It is caused by a wide range of mutations in two genes, PKD1 on chromosome 16p13.3 (85%-90% of cases) or PKD2 on chromosome 4q21 (10%-15% of cases). A small subset of patients don’t carry either mutation, suggesting the possibility of a third locus (PKD3). About 25% of patients have no family history and represent new mutations.
PKD1 encodes polycystin-1 – a transmembrane glycoprotein receptor involved in cell signaling in renal tubular epithelial cells, especially in the distal nephron. PKD2 encodes polycystin-2 which is expressed throughout the renal tubules and in many extrarenal tissues. It functions as a sodium/calcium ion channel and regulates intracellular calcium levels. Phenotypically, PKD1- and PKD2-mutated cases are similar; however, PKD2 mutations produce milder disease with older age at diagnosis and later onset of hypertension and renal failure. The pathophysiology of polycystin mutations is discussed in the next image. This composite specimen photograph shows bilateral renal involvement with ADPKD. The external surface is studded with numerous cysts ranging in size from a few mm. to 2 cm.
PKD1 encodes polycystin-1 – a transmembrane glycoprotein receptor involved in cell signaling in renal tubular epithelial cells, especially in the distal nephron. PKD2 encodes polycystin-2 which is expressed throughout the renal tubules and in many extrarenal tissues. It functions as a sodium/calcium ion channel and regulates intracellular calcium levels. Phenotypically, PKD1- and PKD2-mutated cases are similar; however, PKD2 mutations produce milder disease with older age at diagnosis and later onset of hypertension and renal failure. The pathophysiology of polycystin mutations is discussed in the next image. This composite specimen photograph shows bilateral renal involvement with ADPKD. The external surface is studded with numerous cysts ranging in size from a few mm. to 2 cm.