Rotor-type hyperbilirubinaemia has no defect in the canalicular bilirubin export pump.
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.
Hrebícek
Martin
M
Institute of Inherited Metabolic Diseases, Charles University 1st Faculty of Medicine, Prague, Czech Republic.
Jirásek
Tomás
T
Hartmannová
Hana
H
Nosková
Lenka
L
Stránecký
Viktor
V
Ivánek
Robert
R
Kmoch
Stanislav
S
Cebecauerová
Dita
D
Vítek
Libor
L
Mikulecký
Miroslav
M
Subhanová
Iva
I
Hozák
Pavel
P
Jirsa
Milan
M
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
D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013448:Sulfobromophthalein; C000715087:ABCC2 protein, human