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A Spectrum of Mutations in the Second Gene for Autosomal Dominant Polycystic Kidney Disease (PKD2)

1997; Elsevier BV; Volume: 61; Issue: 3 Linguagem: Inglês

10.1086/515497

1537-6605

Barbera Veldhuisen, Jasper J. Saris, Simone de Haij, Tomohito Hayashi, David M. Reynolds, Toshio Mochizuki, R Elles, Ragnheiður Fossdal, Nadja Bogdanova, Marjan A. van Dijk, Eliécer Coto, David Ravine, Søren Nørby, C. Verellen‐Dumoulin, M.H. Breuning, Stefan Somlo, Dorien J.M. Peters,

Genetic Syndromes and Imprinting

Recently the second gene for autosomal dominant poly-ADPKD is a genetically heterogeneous disease that cystic kidney disease (ADPKD), located on chromosome can be caused by an alteration in at least three differ-4q21-q22, has been cloned and characterized.The gene ent genes.In 85% of families, the disease is caused by encodes an integral membrane protein, polycystin-2, a mutation in the PKD1 gene, located on chromosome that shows amino acid similarity to the PKD1 gene prod-16p13.3(Reeders et al. 1985; Peters and Sandkuijl uct and to the family of voltage-activated calcium (and 1992).The gene was identified in 1994, and the gene sodium) channels.We have systematically screened the product, polycystin-1, is predicted to be a transmemgene for mutations by single-strand conformation-polybrane protein involved in cell-cell or cell-matrix intermorphism analysis in 35 families with the second type action (The European Polycystic Kidney Disease Conof ADPKD and have identified 20 mutations.So far, sortium 1994; Hughes et al. 1995; The American most mutations found seem to be unique and occur PKD1 Consortium 1995; The International Polycystic throughout the gene, without any evidence of clustering.Kidney Disease Consortium 1995).Recently the In addition to small deletions, insertions, and substitu-PKD2 gene, located on chromosome 4q21-q22 (Kimtions leading to premature translation stops, one amino berling et al. 1993;Peters et al. 1993), has been cloned acid substitution and five possible splice-site mutations and characterized (Mochizuki et al. 1996).Mutations have been found.These findings suggest that the first in this gene are responsible for the disease in Ç15% of step toward cyst formation in PKD2 patients is the loss the families (authors' unpublished observation).The of one functional copy of polycystin-2.gene consists of 15 exons with an open reading frame of 2,904 bp and a 3 UTR of 2,086 bp (Mochizuki et al. 1996).The PKD2 gene product, polycystin-2, is