title: 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.
authors.affiliation: The Department of Medicine, Division of Gastroenterology and Hepatology, University Medical Center, St. Radboud, Nijmegen, The Netherlands. JoostPHDrenth@CS.com
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: Rene H M
authors.initials: RH
authors.lastname: te Morsche
authors.forename: Renate
authors.initials: R
authors.lastname: Smink
authors.forename: Juan S
authors.initials: JS
authors.lastname: Bonifacino
authors.forename: Jan B M J
authors.initials: JB
authors.lastname: Jansen
mesh_terms: D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D018095:Germ-Line Mutation; D005959:Glucosidases; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009426:Netherlands; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D004247:DNA; D005959:Glucosidases; C070368:PRKCSH protein, human