When examined in model cell lines, genetic mutations in the BSEP gene impair its targeting and transport function, contributing to the pathogenesis of progressive familial intrahepatic cholestasis type II (PFIC II).
Progressive familial intrahepatic cholestasis type 2 (PFIC2) is due to mutations in ABCB11 encoding the canalicular bile salt export pump (BSEP) of hepatocyte.
Progressive familial intrahepatic cholestasis type 2 (PFIC-2) is caused by mutations of the bile salt export pump (BSEP [ABCB11]), an ATP-binding cassette (ABC)-transporter exclusively expressed at the canalicular membrane of hepatocytes.
As one type of inherited intrahepatic cholestasis, progressive familial intrahepatic cholestasis type 2 (PFIC2) is caused by pathogenic mutations in the ABCB11 gene, HRM was used to detect mutations in the ABCB11 gene in the present study, and the diagnosis for PFIC2 was made by comprehensive analysis of genetic findings and clinical features.
Mutations in ABCB11, the gene encoding BSEP, induce progressive familial intrahepatic cholestasis type 2 (PFIC2), which presents with severe jaundice and liver dysfunction.
oligonucleotide array CGH identified intragenic exonic deletions in 2 cases: a heterozygous single-exon deletion of 4.5 kb in the SLC25A13 gene [solute carrier family 25, member 13 (citrin)] in an individual with citrin deficiency and a homozygous 10.5-kb deletion of exons 13-17 in the ABCB11 gene [PFIC2, ATP-binding cassette, sub-family B (MDR/TAP), member 11] in a patient with progressive familial intrahepatic cholestasis.
A combination of denaturing high-performance liquid chromatography (DHPLC) and direct sequencing was used to screen ABCB11 mutations in 18 Taiwanese patients with low gamma-glutamyltransferase PFIC or benign recurrent intrahepatic cholestasis (BRIC).
Progressive familial intrahepatic cholestasis type 2 (PFIC2) results from genetic defects of the hepatobiliary bile salt export pump (BSEP, ABCB11) at chromosome 2q24.
FIC1-defective progressive familial intrahepatic cholestasis (previously Byler disease) is determined by mutations in the FIC1 gene, coding for P-type ATPases of unknown physiological function, while a second form (bile salt export pump defective progressive familial intrahepatic cholestatis) is caused by a defective function of the canalicular bile salt export pump.
Additionally, rare monogenetic diseases exist which can be explained by absence of function or dysfunction of specific hepatic transporters, such as progressive familial intrahepatic cholestasis type 2 by genetic modifications in BSEP that lead to a loss of transporter function.
We reviewed the explant livers of seven children with metabolic disorders [ornithine-transcarbamylase deficiency (one), coagulation factor VII deficiency (three), Crigler-Najjar syndrome (one), progressive familial intrahepatic cholestasis type 2 (PFIC-2) deficiency (two)] who received allograft hepatocytes by intraportal infusion with improvement in phenotype, although all later underwent liver transplantation (LT).
We developed a denaturing high-performance liquid chromatography (DHPLC) method to screen patients with PFIC for mutations in ATP8B1 and ABCB11, and combined genetic analyses with immunolabeling in liver for the ABCB11 and ABCB4 gene products.
Thus, it has been recognized that while mutations in the gene encoding BSEP are responsible for a subgroup of progressive familial cholestasis (progressive familial intrahepatic cholestasis subtype 2), a pediatric cholestatic disorder that may progress to cirrhosis, defective expression or function of BSEP may underlie some forms of drug-induced cholestasis.
Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a result of mutations in ABCB11 encoding bile salt export pump (BSEP), the canalicular bile salt export pump of hepatocyte.