Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome.
Gastroenterology
; 117(3): 653-60, 1999 Sep.
Article
em En
| MEDLINE
| ID: mdl-10464142
ABSTRACT
BACKGROUND & 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 approximately 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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
/
Genes MDR
/
Subfamília B de Transportador de Cassetes de Ligação de ATP
/
Proteínas Associadas à Resistência a Múltiplos Medicamentos
/
Icterícia Idiopática Crônica
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article