A GENE ENCODING A LIVER-SPECIFIC ABC TRANSPORTER IS MUTATED IN PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS

The progressive familiar intrahepatic cholestases (PFIC) are a group o f inherited disorders with severe cholestatic liver disease from early infancy. A subgroup characterized by normal serum cholesterol and gam ma-glutamyltranspeptidase (gamma GT) levels is genetically heterogeneo us with loci on chromosomes 2q (PFIC2) and 18q. The phenotype of the P FIC2-linked group is consistent with defective bile acid transport at the hepatocyte canalicular membrane. The PFIC2 gene has now been ident ified by mutations in a positional candidate, BSEP, which encodes a li ver-specific ATP-binding cassette (ABC) transporter, sister of p-glyco protein (SPGP). The product of the orthologous rat gene has been shown to be an effective bile acid transporter in vitro. These data provide evidence that SPCP is the human bile salt export pump (BSEP).