Is there a third gene for autosomal dominant polycystic kidney disease?

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a common Mendelian disorder. Linkage studies have estimated that 80 to 85% of cases of ADPKD are due to PKD1 mutations, while most of the remaining cases are due to PKD2 mutations1. In the past three years, five pedigrees with ADPKD have been reported to be unlinked to both of these genes. These families have different geographic origins: Canada2, Portugal3, Bulgaria4, Italy5, and Spain6, and have led to the suggestion of at least one additional gene for ADPKD (PKD3). While the presence of an as yet unmapped disease gene can explain the absence of linkage in these families to the known genes for ADPKD, the converse may not be true. In this commentary, we shall consider the potential confounders that could lead to false exclusion of these putative families from linkage to the known genes. Excluding these confounders are crucial to ensure that the unlinked families are indeed due to mutations in a novel gene. Otherwise, a genome-wide search for PKD3 may be premature.