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

Nature Genetics volume 33, pages 345–347 (2003)Cite this article

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.

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

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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.

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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

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  1. Joost P.H. Drenth
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  2. Rene H.M. te Morsche
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  3. Renate Smink
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  4. Juan S. Bonifacino
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  5. Jan B.M.J. Jansen
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Correspondence to Joost P.H. Drenth.

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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

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