MUTATIONS IN THE CANALICULAR MULTISPECIFIC ORGANIC ANION TRANSPORTER (CMOAT) GENE, A NOVEL ABC TRANSPORTER, IN PATIENTS WITH HYPERBILIRUBINEMIA-II DUBIN-JOHNSON-SYNDROME

Members of the ATP-binding cassette (ABC) transporter superfamily are mutated to cause diseases that include cystic fibrosis, hyperinsulinem ia, adrenoleukodystrophy, Stargardt disease and multidrug resistance, We recently isolated a novel human member of ABC transporter superfami ly as the candidate transporter for the glucuronide and glutathione-co njugated antitumor agents, and found it highly homologous to the rat c moat gene, Consistent with recent findings of defects in the homologou s cmoaf gene in two rat models of hyperbilirubinemia (TR- and Eisai), we report two deletions and a missense mutation in the active transpor t family signature region in the gene in patients with hyperbilirubine mia II/Dubin-Johnson syndrome (DJS; MIM 237500), respectively, These r esults strongly implicate the cMOAT gene as responsible for the defect s in DJS patients.