title: Cholestatic liver diseases from child to adult: the diversity of MDR3 disease.
abstract: The phospholipidfloppase MDR3 (gene symbol: ABCB4) is expressed in the canalicular membrane of hepatocytes and mediates the biliary excretion of phosphatidylcholine, which is required for the formation of mixed micelles in bile. Several mutations of ABCB4 have been identified, which cause cholestatic liver diseases of varying severity including progressive familial intrahepatic cholestasis type 3 (PFIC-3), intrahepatic cholestasis of pregnancy (ICP) and the low phospholipid associated cholelithiasis syndrome (LPAC). Here, we report on four new (S1076N; L 23Hfs16X; c.286 + 1G > A; Q 1181E) and one known (S27G) MDR3 mutations in eight patients of three families. The patients presented with a wide spectrum of liver diseases. The clinical presentation and decisive laboratory findings or the association to a trend-setting family history led to the identification of the genetic background in these patients. Even the same mutation may be associated with varying disease progression.
authors.affiliation: Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf. Kubitz@med.uni-duesseldorf.de
authors.forename: R
authors.initials: R
authors.lastname: Kubitz
authors.forename: J
authors.initials: J
authors.lastname: Bode
authors.forename: A
authors.initials: A
authors.lastname: Erhardt
authors.forename: D
authors.initials: D
authors.lastname: Graf
authors.forename: G
authors.initials: G
authors.lastname: Kircheis
authors.forename: I
authors.initials: I
authors.lastname: Müller-Stöver
authors.forename: R
authors.initials: R
authors.lastname: Reinehr
authors.forename: S
authors.initials: S
authors.lastname: Reuter
authors.forename: J
authors.initials: J
authors.lastname: Richter
authors.forename: A
authors.initials: A
authors.lastname: Sagir
authors.forename: M
authors.initials: M
authors.lastname: Schmitt
authors.forename: M
authors.initials: M
authors.lastname: Donner
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000328:Adult; D000375:Aging / Q000235:genetics*; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; C095122:multidrug resistance protein 3