König J (1999)
Publication Type: Journal article
Publication year: 1999
Book Volume: 117
Pages Range: 653-660
Journal Issue: 3
DOI: 10.1016/S0016-5085(99)70459-2
Background and Aims: The Dubin-Johnson syndrome is characterized by conjugated hyperbilirubinemia and by impaired secretion of anionic conjugates from hepatocytes into bile. Absence of the multidrug-resistance protein 2 (MRP2; symbol ABCC2), an adenosine triphosphate-dependent conjugate export pump, from the hepatocyte canalicular membrane is the molecular basis of this syndrome. The aim of this study was the elucidation of all exon-intron boundaries of the MRP2 gene as a prerequisite for the analysis of mutations in patients with Dubin-Johnson syndrome. Methods: Exon-intron boundaries of MRP2 were determined, and the amplified exons were screened for mutations. Immunofluorescence microscopy served to localize the MRP2 protein in human liver. Results: The human MRP2 gene is ~45 kilobases long; it contains 32 exons and a high proportion of class 0 introns. In 2 patients with Dubin- Johnson syndrome, we detected a nonsense mutation at codon 1066 and a 6- nucleotide deletion mutation affecting codons 1392-1394. The MRP2 protein was absent from the canalicular membrane of both patients. Conclusions: The mutations detected so far show that various mutations in the MRP2 gene can lead to the Dubin-Johnson syndrome. The exon-intron boundaries established in this article will facilitate the analysis of additional mutations in the MRP2 gene.
APA:
König, J. (1999). Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome. Gastroenterology, 117(3), 653-660. https://doi.org/10.1016/S0016-5085(99)70459-2
MLA:
König, Jörg. "Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome." Gastroenterology 117.3 (1999): 653-660.
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