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

JPH Drenth, RHM te Morsche, R Smink, JS Bonifacino… - Nature …, 2003 - nature.com
JPH Drenth, RHM te Morsche, R Smink, JS Bonifacino, JBMJ Jansen
Nature genetics, 2003nature.com
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 (Z max= 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 …
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 (Z max= 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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