Functional characterization of ABCB4 mutations found in progressive familial intrahepatic cholestasis type 3

Functional characterization of ABCB4 mutations found in progressive familial intrahepatic cholestasis type 3

Multidrug resistance 3 (MDR3), encoded by the ATP-binding cassette, subfamily B, member 4 gene (ABCB4), localizes to the canalicular membrane of hepatocytes and translocates phosphatidylcholine from the inner leaflet to the outer leaflet of the canalicular membrane. Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare hepatic disease caused by genetic mutations of ABCB4. In th...

Progressive Familial Intrahepatic Cholestasis

Progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal-recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and associated with mutations ...

Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis.

Class III multidrug resistance (MDR) P-glycoproteins (P-gp), mdr2 in mice and MDR3 in man, mediate the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte. Mice with a disrupted mdr2 gene completely lack biliary phospholipid excretion and develop progressive liver disease, characterized histologically by portal inflammation, proliferation of the bile duct epit...

Pancreatic adenocarcinoma in type 2 progressive familial intrahepatic cholestasis

BACKGROUND BSEP disease results from mutations in ABCB11, which encodes the bile salt export pump (BSEP). BSEP disease is associated with an increased risk of hepatobiliary cancer. CASE PRESENTATION A 36 year old woman with BSEP disease developed pancreatic adenocarcinoma at age 36. She had been treated with a biliary diversion at age 18. A 1.7 x 1.3 cm mass was detected in the pancreas on ab...