Disease relevance of Jaundice, Chronic Idiopathic

• This phenotype is similar to human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury [1].
• MRP2 is the major transporter responsible for the secretion of bilirubin glucuronides into bile, and humans without MRP2 develop a mild liver disease known as the Dubin-Johnson syndrome [2].
• The nicotinic acid test was performed in 5 patients with Dubin-Johnson syndrome, 5 with Rotor syndrome and 13 with Gilbert's syndrome [3].
• While the preoperative serum bilirubin level is one of the established criteria for determining the indications for a hepatic resection, it is not effective for HCV cirrhosis cases associated with Dubin-Johnson syndrome [4].
• Neonatal Dubin-Johnson syndrome with severe cholestasis: effective phenobarbital therapy [5].

High impact information on Jaundice, Chronic Idiopathic

• Our study indicates that bilirubin glucuronides are primarily secreted into the bile canaliculus by an ATP-dependent mechanism which is defective in an animal model of the human Dubin-Johnson syndrome [6].
• Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome [7].
• As the area under the curve reflects the hepatic clearance of intestinally absorbed ursodeoxycholic acid and therefore gives a quantitative estimate of hepatic ursodeoxycholic acid clearance, the hepatic clearance of ursodeoxycholic acid seems to be impaired in patients with Gilbert's syndrome and Dubin-Johnson syndrome [8].
• Bile acid excretion in Dubin-Johnson syndrome [9].
• The defect in TR- mutant rats is phenotypically similar to that seen in mutant Corriedale sheep and in the Dubin-Johnson syndrome in man [10].

Chemical compound and disease context of Jaundice, Chronic Idiopathic

• This is the first mutation in Dubin-Johnson syndrome shown to cause deficient MRP2 maturation and impaired sorting of this glycoprotein to the apical membrane [11].
• Serum bile salt measurements and intravenous clearance of glycocholate were performed in a woman with Dubin-Johnson syndrome [12].
• Dubin-Johnson syndrome (DJS), a congenital metabolic disorder of bilirubin excretion, was classically diagnosed by the bromsulfalein (BSP) curve and needle hepatic biopsy methods [13].
• In this work, we analyzed a relatively frequent Dubin-Johnson syndrome mutation that leads to an exchange of two hydrophobic amino acids, isoleucine 1173 to phenylalanine (MRP2I1173F), in a predicted extracellular loop of MRP2 [14].
• The effect of phenobarbital on patients with Dubin-Johnson syndrome [15].

Biological context of Jaundice, Chronic Idiopathic

• The elucidation of the selective absence of an isoform of MRP and from the canalicular membrane domain in conjunction with the defined substrate specificity of the MRP and cMRP gene-encoded conjugate export pumps contributes to the molecular definition of the transport defect in Dubin-Johnson syndrome [16].

Anatomical context of Jaundice, Chronic Idiopathic

• A particularly strong expression of the MRP3 protein was observed in the basolateral hepatocyte membrane of two patients with Dubin-Johnson syndrome who are deficient in MRP2 [17].

Gene context of Jaundice, Chronic Idiopathic

• MRP1 is a ubiquitously expressed efflux pump for the products of phase II of xenobiotic detoxification, while MRP2, whose hereditary deficiency results in Dubin-Johnson syndrome, functions to extrude organic anions into the bile [18].
• Moreover, Mrp2 (Abcc2) deficient animals display mild conjugated hyperbilirubinemia, corresponding to a human condition known as Dubin-Johnson syndrome (DJS) [19].
• Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome [20].
• The absence of this canalicular Mrp in the mutants is analogous to the defect in the human Dubin-Johnson syndrome which is characterized by an impaired excretion of conjugated anions across the canalicular membrane [21].
• MRP2 is not expressed in the human Dubin-Johnson syndrome, which is therefore associated with an inherited deficiency in the secretion of amphiphilic anionic conjugates into the bile [22].

Analytical, diagnostic and therapeutic context of Jaundice, Chronic Idiopathic

• A 72-year-old woman with hepatocellular carcinoma and HCV cirrhosis combined with Dubin-Johnson syndrome was successfully treated by a central bilateral segmentectomy [4].

References