First, large genomic deletions that affect both TSC2 and the adjacent PKD1 gene lead to early-onset, severe polycystic kidney disease.13 Second, there are a number of missense mutations in TSC2 that are associated with a relatively mild phenotype.42, 43, 44 However, these two types of mutation currently account for <5% of reported TSC gene mutations. This evidence concerns the gene PKD1 and polycystic kidney disease.