Several genes have been identified in autosomal-dominant PKD (ADPKD). The most commonly affected genes are PKD1 or PKD2. (1)
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. (2)
A second causative gene, ADPKD2, was been identified and localised to chromosome 4. (2)
- 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 sensor, regulating the differentiation and proliferation of tubular epithelial cells.
A family history of ADPKD is not apparent in 10% to 25% of patients with ADPKD (3) and despite comprehensive screening, 10% to 15% of patients suspicious of ADPKD have no mutation detected in either PKD1 or PKD2 (4)
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.
- Harris PC, Torres VE. Polycystic kidney disease, autosomal dominant. GeneReviews. July 2018 [internet publication].
- Iliuta IA, Kalatharan V, Wang K, et al. Polycystic kidney disease without an apparent family history. J Am Soc Nephrol. 2017 Sep;28(9):2768-76.
- Lanktree MB, Haghighi A, di Bari I, et al. Insights into autosomal dominant polycystic kidney disease from genetic studies. Clin J Am Soc Nephrol. 2021 May 8;16(5):790-9.