Autosomal Dominant Polycystic Kidney Disease Somatic Mutation Biorepository

The presentation of ADPKD renal and extrarenal manifestations varies widely, even within families, and has been attributed to numerous genetic factors. One principal explanation came with the discovery that renal cyst lining cells from ADPKD patients undergo secondary somatic mutations, selective loss of the second copy of a respective normal polycystic kidney disease (PKD) gene. These somatic mutations can occur in either polycystic kidney disease 1 (PKD1) or polycystic kidney disease 2 (PKD2). Furthermore, various cysts in the same patient have been reported to harbor different somatic mutations. These findings implicated a cellular recessive mechanism for cyst formation in ADPKD, suggesting the possibility that the observed intra-familial variation in disease phenotype may, at least in part, be explained by variation in mutation type, the timing and number of somatic "second-hit" mutations in individual family members affected with the disease. However, there is currently very little known about the cellular genetic mechanism leading to cysts development and very few studies, addressing this issue.