title: Novel mutations identified in the human multidrug resistance-associated protein 2 (MRP2/ABCC2) gene in a Japanese patient with Dubin-Johnson syndrome.
abstract: A 39-year-old Japanese women who has been jaundiced since childhood and indicative of Dubin-Johnson syndrome (DJS) underwent MRP2/ABCC2 mutation analysis. The results of the analysis revealed two novel mutations, C298T and C3928T, and two single nucleotide polymorphisms (SNPs), C3972T and C-24T. One of the two mutations (C298T) is in the transmembrane domain. The other mutation (C3928T) and the SNP (C3972T) are in the cytoplasmaic domain which are concentrated in the second adenosine triphosphate (ATP)-binding cassette. Both of the mutations, C298T and C3928T, are immature stop codons. C298T, C-24T and C3972T (originating from the mother) and C3928T (from the father) were observed to be heterozygous in this patient. Light-microscopy examination of the liver biopsy specimens revealed the accumulation of dark pigment granules in most of the hepatocytes. In the immunohistochemistry using pAb recognizing the C-terminal of the human MRP2, no staining of MRP2 in the canalicular membrane domain was observed in the liver sections from this patient. In this patient, the mutations with immature stop codons presumably resulted in instability of MRP2 mRNA and/or defective synthesis of the truncated protein, which may underlie the loss of the expression of functional MRP2 protein.
authors.affiliation: Department of Gastroenterology, Institute of Clinical Medicine, The University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, 305-8575, Ibaraki, Japan
authors.forename: Junichi
authors.initials: J
authors.lastname: Shoda
authors.forename: Hideo
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hirouchi
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Koji
authors.initials: K
authors.lastname: Oda
authors.forename: Toru
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Naomi
authors.initials: N
authors.lastname: Tanaka