Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP- binding-cassette region in Dubin-Johnson syndrome

Satoshi Toh, Morimasa Wada, Takeshi Uchiumi, Akihiko Inokuchi, Yoshinari Makino, Yutaka Horie, Yukihiko Adachi, Shotaro Sakisaka, Michihiko Kuwano

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Abstract

Dubin-Johnson syndrome (DJS) is an autosomal recessive disease characterized by conjugated hyperbilirubinemia. Previous studies of the defects in the human canalicular multispecific organic anion transporter gene (MRP2/cMOAT) in patients with DJS have suggested that the gene defects are responsible for DJS. In this study, we determined the exon/intron structure of the human MRP2/cMOAT gene and further characterized mutations in patients with DJS. The human MRP2/cMOAT gene contains 32 exons, and it has a structure that is highly conserved with that of another ATP- binding-cassette gene, that for a multidrug resistance-associated protein. We then identified three mutations, including two novel ones. All mutations identified to date are in the cytoplasmic domain, which includes the two ATP-binding cassettes and the linker region, or adjacent putative transmembrane domain. Our results confirm that MRP2/cMOAT is the gene responsible for DJS. The finding that mutations are concentrated in the first ATP- binding-cassette domain strongly suggests that a disruption of this region is a critical route to loss of function.

Original languageEnglish
Pages (from-to)739-746
Number of pages8
JournalAmerican journal of human genetics
Volume64
Issue number3
DOIs
Publication statusPublished - Jan 1 1999

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All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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