Homozygous mutation Arg768 Trp in the ABC-transporter encoding gene MRP2/cMOAT/ABCC2 causes Dubin-Johnson syndrome in a Caucasian patient

Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder characterized by conjugated hyperbilirubinemia and caused by mutations of the ATP-binding cassette (ABC) transporter encoding gene MRP2/cMOAT/ABCC2. Previous studies reported on mutations in DJS patients and polymorphisms in healthy human individuals. The genomic DNA sequence of a female Caucasian DJS patient was analyzed by DNA sequencing and revealed the identification of a homozygous missense mutation C2302T. This DJS-causing alteration results in an amino acid exchange Arg(768)Trp. or the apical membrane of renal proximal tubules (Konig et al. 1999). In the liver, the ABCC2 protein mediates the multispecific efflux of various types of organic anions, including glucuronate, sulfate, and glutathione conjugates., across the canalicular hepatocyte membrane into the bile, dependent on ATP-hydrolysis (Suzuki and Sugiyama 2002). So far, several mutations and polymorphisms of the human ABCC2 gene have been reported (Wada et al. 1998: Toh et al. 1999; Ito et al. 2001; Mor-Cohen et al. 2001, Itoda et al. 2002; Saito et al. 2002). In this study, we report a mutation of the ABCC2 gene in a patient with DJS, which was also described to be a single nucleotide polymorphism (SNP) in healthy specimens by other authors (Ito et al. 2001; Saito et al. 2002). Additionally, the SNP C-24T (NCBI SNP ID rs717620) of the 5'-untranslated region (5'-UTR) in a set of healthy European individuals and a panel of human tumor cell lines was analyzed.