A splice mutation in the human canalicular multispecific organic anion transporter gene causes Dubin-Johnson syndrome

The human Dubin Johnson syndrome (DJS) is a rare autosomal recessive disord er characterized by chronic conjugated hyperbilirubinemia and impaired hepa tobiliary transport of non-bile salt organic anions. A highly homologous ph enotype exists in the transport deficient (TR-) Wistar rat, which has a def ective canalicular multispecific organic anion transporter (cMOAT). This pr otein mediates adenosine triphosphate-dependent transport of a broad range of endogenous and xenobiotic compounds across the (apical) canalicular memb rane of the hepatocyte. The cDNA encoding rat cMOAT has recently been clone d, and this mutation in the TR- rat has been identified. Subsequently the h uman homologue of rat cMOAT localized in the liver was found to be the caus e of DJS. In an individual with DJS, we have identified a single novel nucl eotide substitution in the exon-intron junction of the cMOAT gene which gen erates liver cDNA with a 67bp exon deletion. (C) 1998 Academic Press.