Mutations of the human polycystic kidney disease 2 (PKD2) gene

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited nephro pathy, usually of late onset (onset between third to seventh decade), prima rily characterized by the formation of fluid-filled cysts in the kidneys. I t is one of the most frequent inherited conditions affecting approximately 1:1,000 Caucasians. Two major genes have been identified and characterized in detail: PKD1 and PKD2, mapping on chromosomes 16p13.3 and 4q21-23, respe ctively. A third gene, PKD3, has been implicated in selected families. Poly cystic kidney disease of types 1 or 2 follows a veri similar course of symp toms, both being multisystem pleiotropic disorders of indistinguishable pic ture on clinical grounds. The only difference is that patients with PKD2 mu tations run a milder course compared to PKD1 carriers, with an average 10-2 0 years later age of onset and lower probability to reach end-stage-renal f ailure. The proteins polycystin-1 and -2 are transmembranous glycoproteins hypothesized to participate in a common signaling pathway, interacting with each other and with other proteins, and coordinately expressed in normal a nd cystic tissue. Renal cysts most probably arise after a second somatic ev ent, which inactivates the inherited healthy allele of the same gene, or pe rhaps one of the alleles of the other gene counterpart, generating a trans- heterozygous state. This article reviews the reported mutations in PKD2. Mu tations of all kinds have been reported over the entire sequence of the PKD 2 gene, with no apparent significant clustering and with some evidence of g enotype/phenotype correlation. Most families harbor their own private mutat ions but a few recurrent events have been reported in unrelated families. H um Mutat 18:13-24, 2001. (C) 2001 Wiley-Liss, Inc.