Skip to main content
SpringerLink
Log in

Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease

  • Brief Communication
  • Published:

From Nature Genetics

View current issue Submit your manuscript

Abstract

Polycystic liver disease (PCLD, OMIM 174050) is a dominantly inherited condition characterized by the presence of multiple liver cysts of biliary epithelial origin. Fine mapping established linkage to marker D19S581 (Zmax = 9.65; θ = 0.01) in four large Dutch families with PCLD. We identified a splice-acceptor site mutation (1138–2A→G) in PRKCSH in three families, and a splice-donor site mutation (292+1G→C) in PRKCSH segregated completely with PCLD in another family. The protein encoded by PRKCSH, here named hepatocystin, is predicted to localize to the endoplasmic reticulum. These findings establish germline mutations in PRKCSH as the probable cause of PCLD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1: Haplotype analysis and a graphic representation of multipoint lod scores in PCLD.
Figure 2: Analysis of PRKCSH mutations associated with PCLD.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Qian, Q. et al. Hepatology 37, 164–171 (2003).

    Article  Google Scholar 

  2. Tahvanainen, P. et al. J. Hepatol. 38, 39–43 (2003).

    Article  CAS  Google Scholar 

  3. Reynolds, D.M. et al. Am. J. Hum. Genet. 67, 1598–1604 (2000).

    Article  CAS  Google Scholar 

  4. The European Polycystic Kidney Disease Consortium. Cell 77, 881–894 (1994).

  5. Mochizuki, T. et al. Science 272, 1339–1342 (1996).

    Article  CAS  Google Scholar 

  6. Ward, C.J. et al. Nat. Genet. 30, 259–269 (2002).

    Article  Google Scholar 

  7. Xiong, H. et al. Genomics 80, 96–104 (2002).

    Article  CAS  Google Scholar 

  8. Onuchic, L.F. et al. Am. J. Hum. Genet. 70, 1305–1317 (2002).

    Article  CAS  Google Scholar 

  9. Hirai, M. & Shimizu, N. Biochem. J. 270, 583–589 (1990).

    Article  CAS  Google Scholar 

  10. Sakai, K. et al. Genomics 5, 309–315 (1989).

    Article  CAS  Google Scholar 

  11. Curto, M., Frankel, P., Carrero, A. & Foster, D.A. Biochem. Biophys. Res. Commun. 243, 555–560 (1998).

    Article  CAS  Google Scholar 

  12. Li, Y.M. et al. Proc. Natl. Acad. Sci. USA 93, 11047–11052 (1996).

    Article  CAS  Google Scholar 

  13. Thornalley, P.J. Cell Mol. Biol. (Noisy-le-grand) 44, 1013–1023 (1998).

    CAS  Google Scholar 

  14. Trombetta, E.S., Fleming, K.G. & Helenius, A. Biochemistry 40, 10717–10722 (2001).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the family members for their support and cooperation, Pie Medical for free lending of the mobile ultrasound scanner and H.G. Brunner, M. Boehm and J.C. Zenklusen for advice and inspiring discussions. J.P.H.D. is an Investigator of the Royal Netherlands Academy of Arts and Sciences and recipient of a grant from the Niels Stensen Foundation and of a travel grant from the Netherlands Organisation of Scientific Research. This project was supported in part by an unrestricted educational grant from Schering-Plough Corporation.

Author information

Authors and Affiliations

  1. The Department of Medicine, Division of Gastroenterology and Hepatology, University Medical Center, St. Radboud, Nijmegen, The Netherlands

    Joost P.H. Drenth, Rene H.M. te Morsche, Renate Smink & Jan B.M.J. Jansen

  2. Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Building 18T, Room 101, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Joost P.H. Drenth & Juan S. Bonifacino

Authors
  1. Joost P.H. Drenth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rene H.M. te Morsche
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Renate Smink
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juan S. Bonifacino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jan B.M.J. Jansen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joost P.H. Drenth.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Drenth, J., te Morsche, R., Smink, R. et al. Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease. Nat Genet 33, 345–347 (2003). https://doi.org/10.1038/ng1104

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1104

  • Springer Nature America, Inc.

This article is cited by

Search

Navigation