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