A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2)

Am J Hum Genet. 1997 Sep;61(3):547-55. doi: 10.1086/515497.


Recently the second gene for autosomal dominant polycystic kidney disease (ADPKD), located on chromosome 4q21-q22, has been cloned and characterized. The gene encodes an integral membrane protein, polycystin-2, that shows amino acid similarity to the PKD1 gene product and to the family of voltage-activated calcium (and sodium) channels. We have systematically screened the gene for mutations by single-strand conformation-polymorphism analysis in 35 families with the second type of ADPKD and have identified 20 mutations. So far, most mutations found seem to be unique and occur throughout the gene, without any evidence of clustering. In addition to small deletions, insertions, and substitutions leading to premature translation stops, one amino acid substitution and five possible splice-site mutations have been found. These findings suggest that the first step toward cyst formation in PKD2 patients is the loss of one functional copy of polycystin-2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cell Membrane / chemistry
  • Chromosomes, Human, Pair 4 / genetics
  • DNA Mutational Analysis
  • Exons / genetics
  • Genes / genetics*
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Mutation / genetics*
  • Polycystic Kidney, Autosomal Dominant / genetics*
  • Polymorphism, Genetic
  • Polymorphism, Single-Stranded Conformational
  • RNA Splicing
  • TRPP Cation Channels


  • Membrane Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 2 protein