• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of ajhgLink to Publisher's site
Am J Hum Genet. Sep 1997; 61(3): 547–555.
PMCID: PMC1715954

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

Abstract

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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bear JC, McManamon P, Morgan J, Payne RH, Lewis H, Gault MH, Churchill DN. Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: data for genetic counselling. Am J Med Genet. 1984 May;18(1):45–53. [PubMed]
  • Bear JC, Parfrey PS, Morgan JM, Martin CJ, Cramer BC. Autosomal dominant polycystic kidney disease: new information for genetic counselling. Am J Med Genet. 1992 Jun 1;43(3):548–553. [PubMed]
  • Berget SM. Exon recognition in vertebrate splicing. J Biol Chem. 1995 Feb 10;270(6):2411–2414. [PubMed]
  • Bogdanova N, Dworniczak B, Dragova D, Todorov V, Dimitrakov D, Kalinov K, Hallmayer J, Horst J, Kalaydjieva L. Genetic heterogeneity of polycystic kidney disease in Bulgaria. Hum Genet. 1995 Jun;95(6):645–650. [PubMed]
  • Breuning MH, Snijdewint FG, Brunner H, Verwest A, Ijdo JW, Saris JJ, Dauwerse JG, Blonden L, Keith T, Callen DF, et al. Map of 16 polymorphic loci on the short arm of chromosome 16 close to the polycystic kidney disease gene (PKD1). J Med Genet. 1990 Oct;27(10):603–613. [PMC free article] [PubMed]
  • Chapman AB, Rubinstein D, Hughes R, Stears JC, Earnest MP, Johnson AM, Gabow PA, Kaehny WD. Intracranial aneurysms in autosomal dominant polycystic kidney disease. N Engl J Med. 1992 Sep 24;327(13):916–920. [PubMed]
  • Coto E, Sanz de Castro S, Aguado S, Alvarez J, Arias M, Menéndez MJ, López-Larrea C. DNA microsatellite analysis of families with autosomal dominant polycystic kidney disease types 1 and 2: evaluation of clinical heterogeneity between both forms of the disease. J Med Genet. 1995 Jun;32(6):442–445. [PMC free article] [PubMed]
  • DALGAARD OZ. Bilateral polycystic disease of the kidneys; a follow-up of two hundred and eighty-four patients and their families. Acta Med Scand Suppl. 1957;328:1–255. [PubMed]
  • Daoust MC, Reynolds DM, Bichet DG, Somlo S. Evidence for a third genetic locus for autosomal dominant polycystic kidney disease. Genomics. 1995 Feb 10;25(3):733–736. [PubMed]
  • de Almeida S, de Almeida E, Peters D, Pinto JR, Távora I, Lavinha J, Breuning M, Prata MM. Autosomal dominant polycystic kidney disease: evidence for the existence of a third locus in a Portuguese family. Hum Genet. 1995 Jul;96(1):83–88. [PubMed]
  • Fossdal R, Böthvarsson M, Asmundsson P, Ragnarsson J, Peters D, Breuning MH, Jensson O. Icelandic families with autosomal dominant polycystic kidney disease: families unlinked to chromosome 16p13.3 revealed by linkage analysis. Hum Genet. 1993 Jul;91(6):609–613. [PubMed]
  • Gabow PA. Autosomal dominant polycystic kidney disease--more than a renal disease. Am J Kidney Dis. 1990 Nov;16(5):403–413. [PubMed]
  • Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT, Jones RH. Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int. 1992 May;41(5):1311–1319. [PubMed]
  • Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millán JL, Gamble V, Harris PC. The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat Genet. 1995 Jun;10(2):151–160. [PubMed]
  • Kimberling WJ, Kumar S, Gabow PA, Kenyon JB, Connolly CJ, Somlo S. Autosomal dominant polycystic kidney disease: localization of the second gene to chromosome 4q13-q23. Genomics. 1993 Dec;18(3):467–472. [PubMed]
  • Krawczak M, Reiss J, Cooper DN. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum Genet. 1992 Sep-Oct;90(1-2):41–54. [PubMed]
  • Maquat LE. Defects in RNA splicing and the consequence of shortened translational reading frames. Am J Hum Genet. 1996 Aug;59(2):279–286. [PMC free article] [PubMed]
  • Milutinovic J, Fialkow PJ, Rudd TG, Agodoa LY, Phillips LA, Bryant JI. Liver cysts in patients with autosomal dominant polycystic kidney disease. Am J Med. 1980 May;68(5):741–744. [PubMed]
  • Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ, Reynolds DM, Cai Y, Gabow PA, Pierides A, et al. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science. 1996 May 31;272(5266):1339–1342. [PubMed]
  • Nakai K, Sakamoto H. Construction of a novel database containing aberrant splicing mutations of mammalian genes. Gene. 1994 Apr 20;141(2):171–177. [PubMed]
  • Neophytou P, Constantinides R, Lazarou A, Pierides A, Deltas CC. Detection of a novel nonsense mutation and an intragenic polymorphism in the PKD1 gene of a Cypriot family with autosomal dominant polycystic kidney disease. Hum Genet. 1996 Oct;98(4):437–442. [PubMed]
  • Nørby S, Schwartz M. Possible locus for polycystic kidney disease on chromosome 2. Lancet. 1990 Aug 4;336(8710):323–324. [PubMed]
  • Orita M, Suzuki Y, Sekiya T, Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. [PubMed]
  • Padgett RA, Grabowski PJ, Konarska MM, Seiler S, Sharp PA. Splicing of messenger RNA precursors. Annu Rev Biochem. 1986;55:1119–1150. [PubMed]
  • Parfrey PS, Bear JC, Morgan J, Cramer BC, McManamon PJ, Gault MH, Churchill DN, Singh M, Hewitt R, Somlo S, et al. The diagnosis and prognosis of autosomal dominant polycystic kidney disease. N Engl J Med. 1990 Oct 18;323(16):1085–1090. [PubMed]
  • Peral B, Gamble V, San Millán JL, Strong C, Sloane-Stanley J, Moreno F, Harris PC. Splicing mutations of the polycystic kidney disease 1 (PKD1) gene induced by intronic deletion. Hum Mol Genet. 1995 Apr;4(4):569–574. [PubMed]
  • Peral B, Ong AC, San Millán JL, Gamble V, Rees L, Harris PC. A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1 (PKD1). Hum Mol Genet. 1996 Apr;5(4):539–542. [PubMed]
  • Peral B, San Millán JL, Ong AC, Gamble V, Ward CJ, Strong C, Harris PC. Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene reveals six novel mutations. Am J Hum Genet. 1996 Jan;58(1):86–96. [PMC free article] [PubMed]
  • Peters DJ, Sandkuijl LA. Genetic heterogeneity of polycystic kidney disease in Europe. Contrib Nephrol. 1992;97:128–139. [PubMed]
  • Peters DJ, Spruit L, Saris JJ, Ravine D, Sandkuijl LA, Fossdal R, Boersma J, van Eijk R, Nørby S, Constantinou-Deltas CD, et al. Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease. Nat Genet. 1993 Dec;5(4):359–362. [PubMed]
  • Qian F, Germino FJ, Cai Y, Zhang X, Somlo S, Germino GG. PKD1 interacts with PKD2 through a probable coiled-coil domain. Nat Genet. 1997 Jun;16(2):179–183. [PubMed]
  • Qian F, Watnick TJ, Onuchic LF, Germino GG. The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell. 1996 Dec 13;87(6):979–987. [PubMed]
  • Ravine D, Walker RG, Gibson RN, Forrest SM, Richards RI, Friend K, Sheffield LJ, Kincaid-Smith P, Danks DM. Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney disease. Lancet. 1992 Nov 28;340(8831):1330–1333. [PubMed]
  • Reeders ST. Multilocus polycystic disease. Nat Genet. 1992 Jul;1(4):235–237. [PubMed]
  • Reeders ST, Breuning MH, Davies KE, Nicholls RD, Jarman AP, Higgs DR, Pearson PL, Weatherall DJ. A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature. 1985 Oct 10;317(6037):542–544. [PubMed]
  • Roelfsema JH, Breuning MH. The long walk toward the PKD1 gene. The European PKD1 Consortium. Adv Nephrol Necker Hosp. 1996;25:131–145. [PubMed]
  • Rossetti S, Bresin E, Restagno G, Carbonara A, Corrà S, De Prisco O, Pignatti PF, Turco AE. Autosomal dominant polycystic kidney disease (ADPKD) in an Italian family carrying a novel nonsense mutation and two missense changes in exons 44 and 45 of the PKD1 Gene. Am J Med Genet. 1996 Oct 16;65(2):155–159. [PubMed]
  • Turco AE, Rossetti S, Bresin E, Corra S, Gammaro L, Maschio G, Pignatti PF. A novel nonsense mutation in the PKD1 gene (C3817T) is associated with autosomal dominant polycystic kidney disease (ADPKD) in a large three-generation Italian family. Hum Mol Genet. 1995 Aug;4(8):1331–1335. [PubMed]
  • van Dijk MA, Chang PC, Peters DJ, Breuning MH. Intracranial aneurysms in polycystic kidney disease linked to chromosome 4. J Am Soc Nephrol. 1995 Dec;6(6):1670–1673. [PubMed]
  • Veldhuisen B, Breuning MH, Wesby-van Swaay E, Boersma J, Peters DJ. Analysis of a large family with the second type of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 1996;11 (Suppl 6):13–17. [PubMed]
  • Weissenbach J, Gyapay G, Dib C, Vignal A, Morissette J, Millasseau P, Vaysseix G, Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. [PubMed]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Gene
    Gene
    Gene links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • MedGen
    MedGen
    Related information in MedGen
  • OMIM
    OMIM
    OMIM record citing PubMed
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...