Cell
Volume 77, Issue 6, 17 June 1994, Pages 881-894
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Article
The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16

https://doi.org/10.1016/0092-8674(94)90137-6Get rights and content

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently results in renal fallure due to progressive cyst development. The major locus, PKD1, maps to 16p13.3. We identified a chromosome translocation associated with ADPKD that disrupts a gene (PBP) encoding a 14 kb transcript in the PKD1 candidate region. Further mutations of the PBP gene were found in PKD1 patients, two deletions (one a de novo event) and a splicing defect, confirming that PBP is the PKD1 gene. This gene is located adjacent to the TSC2 locus in a genomic region that is reiterated more proximally on 16p. The duplicate area encodes three transcripts substantially homologous to the PKD1 transcript. Partial sequence analysis of the PKD1 transcript shows that it encodes a novel protein whose function is at present unknown.

References (56)

  • J. Milutinovic et al.

    Liver cysts in patients with autosomal dominant polycystic kidney disease

    Am. J. Med.

    (1980)
  • D. Ravine et al.

    Treatable complications in undiagnosed cases of autosomal dominant polycystic kidney disease

    Lancet

    (1991)
  • D. Ravine et al.

    Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney disease

    Lancet

    (1992)
  • S.T. Reeders et al.

    Regional localization of the autosomal dominant polycystic kidney disease locus

    Genomics

    (1988)
  • S. Somlo et al.

    Fine genetic localization of the gene for autosomal dominant polycystic kidney disease (PKD1) with respect to physically mapped markers

    Genomics

    (1992)
  • A.D. Thompson et al.

    Isolation and characterization of (AC)n microsatellite genetic markers from human chromosome 16

    Genomics

    (1992)
  • P.D. Wilson et al.

    Tubulocystic epithelium

    Kidney Int.

    (1991)
  • I. Aksentijevich et al.

    Refined mapping of the gene causing familial Mediterranean fever, by linkage and homozygosity studies

    Am. J. Hum. Genet.

    (1993)
  • M.H. Breuning 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)
  • C.J. Brown et al.

    X chromosome inactivation of the human TIMP gene

    Nucl. Acids Res.

    (1990)
  • V.J. Buckle et al.

    Fluorescent in situ hybridisation

  • A.B. Chapman et al.

    Intracranial aneurysms in autosomal dominant polycystic kidney disease

    N. Engl. J. Med.

    (1992)
  • O.Z. Dalgaard

    Bilateral polycystic disease of the kidneys: a follow-up of two hundred and eighty-four patients and their families

    Acta Med. Scand. (Suppl.)

    (1957)
  • F. Davies et al.

    Polycystic kidney disease re-evaluated: a population-based study

    Quart. J. Med.

    (1991)
  • A. Deisseroth et al.

    Activation of phenotypic expression of human globin genes from non-erythroid cells by chromo-some-dependent transfer to tetraploid mouse erythroleukemia cells

  • C. Dodé et al.

    Locus assignment of human α globin mutations by selective amplification and direct sequencing

    Br. J. Haemat.

    (1990)
  • European Chromosome 16 Tuberous Sclerosis Consortium

    Identification and characterization of the tuberous sclerosis gene on chromosome 16

    Cell

    (1993)
  • G.M. Fink et al.

    Characteristics of very early onset autosomal dominant polycystic kidney disease

    J. Am. Soc. Nephrol.

    (1993)
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    The European Polycystic Kidney Disease Consortium is comprised of the following groups:

    Group 1: Christopher J. Ward, Belén Peral, Jim Hughes, Sandra Thomas, Vicki Gamble, Angela B. MacCarthy, Jackie Sloane-Stanley, Veronica J. Buckle, Lyndal Kearney, Douglas R. Higgs, Peter J. Ratcliffe, and Peter C. Harris

    Medical Research Council Molecular Haematology Unit Institute of Molecular Medicine John Radcliffe Hospital Headington, Oxford OX3 9DU England

    Group 2: Jeroen H. Roelfsema, Lia Spruit, Jasper J. Saris, Hans G. Dauwerse, Dorien J. M. Peters, and Martijn H. Breuning

    Department of Human Genetics Leiden University 2333 AL Leiden The Netherlands

    Group 3: Mark Nellist,1 Phillip T. Brook-Carter,1 Magitha M. Maheshwar,1 Isabel Cordeiro,2 Heloisa Santos,2 Pedro Cabral,3 and Julian R. Sampson1

    1Institute of Medical Genetics University of Wales College of Medicine Cardiff CF4 4XN Wales

    2Genetics Unit Hospital Santa Maria

    3Department of Neurology Hospital D. Estefânia 1699 Lisbon Portugal

    Group 4: Bart Janssen, Arjenne L. W. Hesseling-Janssen, Ans M. W. van den Ouweland, Bert Eussen, Senno Verhoef, Dick Lindhout, and Dicky J. J. Halley

    Department of Clinical Genetics Erasmus University and University Hospital 3015 GE Rotterdam The Netherlands

    Correspondence should be addressed to Peter C. Harris.

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