title: Benign recurrent intrahepatic cholestasis associated with mutations of the bile salt export pump.
abstract: A young patient with recurrent attacks of intrahepatic cholestasis is described. On the basis of clinical presentation, laboratory findings and genetic analysis, the diagnosis of benign recurrent intrahepatic cholestasis type 2 (BRIC-2) was established. By the use of BSEP-specific antibodies, almost complete absence of BSEP from the canalicular membrane of liver cells was detected in the patient. Two different BSEP mutations were found. One mutation (E186G) had been described in one BRIC-2 case; the second mutation (V444A) is more frequent and has been linked to intrahepatic cholestasis of pregnancy. It is concluded that this form of compound heterozygosity of the BSEP gene reduces the amount of BSEP protein due to protein instability or mis-targeting, which is the underlying reason for reduced bile salt excretion and cholemia.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectiology, Heinrich-Heine University, Düsseldorf, Germany. kubitz@med.uni-duesseldorf.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Kubitz
authors.forename: Verena
authors.initials: V
authors.lastname: Keitel
authors.forename: Sybille
authors.initials: S
authors.lastname: Scheuring
authors.forename: Karl
authors.initials: K
authors.lastname: Köhrer
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000293:Adolescent; D001647:Bile Acids and Salts / Q000378:metabolism*; D001706:Biopsy; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D016623:Ion Pumps / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D016623:Ion Pumps