This case reveals that although PKD1 and TSC2 are adjacent genes and there is likely cross-talk between the PKD1 and TSC2 signalling pathways regulating mTOR, having independent TSC2 and PKD1 mutations can give rise to a milder kidney phenotype than is typical in PKD1/TSC2-CGS cases.
The characteristics of the contiguous PKD1/TSC2 syndrome phenotypes and the data from Krd mice imply that TSC2 and PAX2 may also serve as potential modifiers for the disease severity of autosomal-dominant polycystic kidney disease.
The gene responsible for the human juvenile form of neuronal ceroid lipofuscinosis (CLN3), maps close to TSC2 and PKD1 in humans, and is also syntenic in the dog.