title: A new ABCB11 mutation in two Italian children with familial intrahepatic cholestasis.
abstract: Progressive familial intrahepatic cholestasis (PFIC) syndromes are characterized by defects in transporters of conjugated bile acids into the bile canaliculus. Three genes (ATP8B1, ABCB11, ABCB4) are associated with the different forms, but no easy genotype-phenotype correlations help in the prioritization for gene testing. 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. Used in combination with commercially available antibodies on liver specimens, the DHPLC approach allowed us to confirm the clinical diagnosis in two Italian sisters and to identify a novel missesnse mutation in ABCB11. Our findings are expected to facilitate detection of the molecular cause of PFIC in affected families.
authors.affiliation: Hepatology, IRCCS Bambino Gesù Hospital, Piazza S. Onofrio, 4-00165, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Giandomenico
authors.forename: Paola
authors.initials: P
authors.lastname: Francalanci
authors.forename: Francesco
authors.initials: F
authors.lastname: Callea
authors.forename: Matilde
authors.initials: M
authors.lastname: Marcellini
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007558:Italy; D009154:Mutation; D010375:Pedigree
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters