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

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; theta = 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.