title: A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome.
abstract: The human Dubin-Johnson syndrome (DJS) is a rare autosomal recessive liver disorder characterized by chronic conjugated hyperbilirubinemia. Patients have impaired hepatobiliary transport of non-bile salt organic anions. A highly similar phenotype has been described for a mutant Wistar rat strain, the transport-deficient (TR-) rat, which is defective in the canalicular multispecific organic anion transporter (cmoat). This protein mediates adenosine triphosphate-dependent transport of a broad range of endogenous and xenobiotic compounds across the (apical) canalicular membrane of the hepatocyte. The complementary DNA (cDNA) encoding rat cmoat has recently been cloned, and the mutation underlying the defect in TR- rats has been identified. In the present study, we have isolated the human homologue of rat cmoat, human cMOAT, and analyzed the corresponding cDNA from fibroblasts of a DJS patient for mutations. Our results show that a mutation in this gene is the cause of DJS.
authors.affiliation: Department of Gastrointestinal and Liver Diseases, Center for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: C C
authors.initials: CC
authors.lastname: Paulusma
authors.forename: M
authors.initials: M
authors.lastname: Kool
authors.forename: P J
authors.initials: PJ
authors.lastname: Bosma
authors.forename: G L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: F
authors.initials: F
authors.lastname: ter Borg
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: G N
authors.initials: GN
authors.lastname: Tytgat
authors.forename: P
authors.initials: P
authors.lastname: Borst
authors.forename: F
authors.initials: F
authors.lastname: Baas
authors.forename: R P
authors.initials: RP
authors.lastname: Oude Elferink
mesh_terms: D000595:Amino Acid Sequence; D027321:Anion Transport Proteins; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005796:Genes; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007566:Jaundice, Chronic Idiopathic / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D012016:Reference Values; D014018:Tissue Distribution
chemical_list: D027321:Anion Transport Proteins; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D018076:DNA, Complementary