title: Severe Polycystic Liver Disease Is Not Caused by Large Deletions of the PRKCSH Gene.
abstract: BACKGROUND
  Isolated polycystic liver disease (ADPLD) is an autosomal dominant Mendelian disorder. Heterozygous PRKCSH (where PRKCSH is protein kinase C substrate 80K-H (80 kDa protein, heavy chain; MIM*177060) mutations are the most frequent cause. Routine molecular testing using Sanger sequencing identifies pathogenic variants in the PRKCSH (15%) and SEC63 (where SEC63 is Saccharomyces cerevisiae homolog 63 (MIM*608648); 6%) genes, but about approximately 80% of patients meeting the clinical ADPLD criteria carry no PRKCSH or SEC63 mutation. Cyst tissue often shows somatic deletions with loss of heterozygosity that was recently recognized as a general mechanism in ADPLD. We hypothesized that germline deletions in the PRKCSH gene may be responsible for hepatic cystogenesis in a significant number of mutation-negative ADPLD patients.
  
  
  METHODS
  In this study, we designed a multiplex ligation-dependent probe amplification (MLPA) assay to screen for deletions of PRKCSH exons. Genomic DNA from 60 patients with an ADPLD phenotype was included.
  
  
  RESULTS
  MLPA analysis detected no exon deletions in mutation-negative ADPLD patients.
  
  
  CONCLUSIONS
  Large copy number variations on germline level are not present in patients with a clinical diagnosis of ADPLD. MLPA analysis of the PRKCSH gene should not be considered as a diagnostic method to explain hepatic cystogenesis.
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Wybrich R
authors.initials: WR
authors.lastname: Cnossen
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jake S F
authors.initials: JS
authors.lastname: Maurits
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.|Laboratory of Gastroenterology and Hepatology, ADPLD Diagnostics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jody
authors.initials: J
authors.lastname: Salomon
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.|Laboratory of Gastroenterology and Hepatology, ADPLD Diagnostics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: René H M
authors.initials: RH
authors.lastname: Te Morsche
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Esmé
authors.initials: E
authors.lastname: Waanders
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands. joostphdrenth@cs.com.
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
mesh_terms: D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins; D003560:Cysts / Q000235:genetics*; D005260:Female; D005959:Glucosidases / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008107:Liver Diseases / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D018832:Molecular Chaperones; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods; D016601:RNA-Binding Proteins; D012189:Retrospective Studies; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D016601:RNA-Binding Proteins; C487464:SEC63 protein, human; D005959:Glucosidases; C070368:PRKCSH protein, human
keywords: ADPLD; PRKCSH; MLPA; exon deletion; genetic heterogeneity; hepatic cystogenesis