title: Rotor-type hyperbilirubinaemia has no defect in the canalicular bilirubin export pump.
abstract: BACKGROUND
  The cause of Rotor syndrome (RS), a rare-familial conjugated hyperbilirubinaemia with normal liver histology, is unclear. We hypothesized that RS can be an allelic variant of Dubin-Johnson syndrome, caused by mutation in ABCC2, and investigated ABCC2 (gene) and ABCC2 (protein) in two patients with RS.
  
  
  METHODS
  A 57-year-old male presented with a 5-year history of predominantly conjugated hyperbilirubinaemia (170 micromol/l). Urinary porphyrin excretion was increased; cholescintigraphy revealed no chromoexcretion. A 68-year-old male presented with lifelong conjugated hyperbilirubinaemia (85 micromol/l). Bromosulfophthalein elimination was typical for RS. Both patients had histologically normal liver, without pigment. ABCC2 expression was investigated by confocal fluorescence microscopy. ABCC2 was sequenced from genomic DNA and cDNA, and exon deletions/duplications were sought by comparative genomic hybridization on a custom micro-array.
  
  
  RESULTS
  In both patients, ABCC2 was expressed unremarkably at the apical membrane of hepatocytes and no sequence alterations were found in 32 exons, adjacent intronic regions and the promoter region of ABCC2.
  
  
  CONCLUSIONS
  Rotor-type hyperbilirubinaemia is not an allelic variant of ABCC2 deficiency.
authors.affiliation: Institute of Inherited Metabolic Diseases, Charles University 1st Faculty of Medicine, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Hrebícek
authors.forename: Tomás
authors.initials: T
authors.lastname: Jirásek
authors.forename: Hana
authors.initials: H
authors.lastname: Hartmannová
authors.forename: Lenka
authors.initials: L
authors.lastname: Nosková
authors.forename: Viktor
authors.initials: V
authors.lastname: Stránecký
authors.forename: Robert
authors.initials: R
authors.lastname: Ivánek
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kmoch
authors.forename: Dita
authors.initials: D
authors.lastname: Cebecauerová
authors.forename: Libor
authors.initials: L
authors.lastname: Vítek
authors.forename: Miroslav
authors.initials: M
authors.lastname: Mikulecký
authors.forename: Iva
authors.initials: I
authors.lastname: Subhanová
authors.forename: Pavel
authors.initials: P
authors.lastname: Hozák
authors.forename: Milan
authors.initials: M
authors.lastname: Jirsa
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis; D005192:Family Health; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D007566:Jaundice, Chronic Idiopathic; D008099:Liver / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis / Q000235:genetics*; D013448:Sulfobromophthalein / Q000032:analysis
chemical_list: D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013448:Sulfobromophthalein; C000715087:ABCC2 protein, human