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Rotor‐type hyperbilirubinaemia has no defect in the canalicular bilirubin export pump
Author(s) -
Hřebíček Martin,
Jirásek Tomáš,
Hartmannová Hana,
Nosková Lenka,
Stránecký Viktor,
Ivánek Robert,
Kmoch Stanislav,
Cebecauerová Dita,
Vítek Libor,
Mikulecký Miroslav,
Subhanová Iva,
Hozák Pavel,
Jirsa Milan
Publication year - 2007
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2007.01446.x
Subject(s) - multidrug resistance associated protein 2 , exon , biology , compound heterozygosity , mutation , genetics , microbiology and biotechnology , pathology , medicine , gene , atp binding cassette transporter , transporter
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 μmol/l). Urinary porphyrin excretion was increased; cholescintigraphy revealed no chromoexcretion. A 68‐year‐old male presented with lifelong conjugated hyperbilirubinaemia (85 μmol/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.