Genetics

The ADPKD1 gene is located on the short arm of chromosome 16 and appears to be causative in more than 90% of families in the white population. It appears to encode an extracellular matrix protein which is expressed around cerebral, renal and hepatic blood vessels.

A second causative gene, ADPKD2, was been identified and localised to chromosome 4.

• ADPKD is caused by mutations at two genes, PKD1 (16p13.3) and PKD2 (4q21)
  
  
• PKD1 mutations account for approximately 85% and PKD2 mutations for approximately 15% of the cases in clinically well characterized cohorts
  
  
• PKD1 patients reach ESRD approximately 20 years earlier than PKD2 patients (approximately 54 versus 74 years)
  
  
• PKD1 and PKD2 encode polycystin 1 and 2 (PC-1 and PC-2), respectively. PC-1 is a large, transmembrane protein that interacts with PC-2, a transient receptor potential channel that regulates intracellular calcium
  • both proteins localize to the kidney primary cilium, and may act as a flow-dependent mechanosensor regulating the differentiation and proliferation of tubular epithelial cells.

Reference:

• Rossetti S, Consugar MB, Chapman AB, Torres VE, Guay-Woodford LM, Grantham JJ, Bennett WM, Meyers CM, Walker DL, Bae K, Zhang QJ, Thompson PA, Miller JP, Harris PC, CRISP Consortium : Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2007;18: 2143-2160.
• Ravine D, Walker RG, Gibson RN, Forrest SM, Richards RI, Friend K, Sheffield LJ, Kincaid-Smith P, Danks DM.: Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney disease. Lancet 1992;340: 1330-1333.