Characterization of mutations inATP8B1associated with hereditary cholestasis

Novel Resequencing Chip Customized to Diagnose Mutations in Patients With Inherited Syndromes of Intrahepatic Cholestasis

“…For example, although mutations in ATP8B1 and ABCB11 have been reported for subjects with severe forms of PFIC with low serum levels of gamma-glutamyltranspeptide (γGTP), specific mutations within each gene have also been associated with milder clinical phenotypes. 15,17,[24][25][26][27][28][29][30] Equally notable is the phenotypic pleomorphism of mutations in ABCB4, which ranges from high γGTP-PFIC (or PFIC3), to intrahepatic cholestasis of pregnancy, and gallstone formation, 19,25,[31][32][33][34][35][36] and an array of mutations in JAG1 in subjects with liver and/or non-hepatic malformations (e.g. : cardiovascular and renal defects).…”

Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport

“…4D) are homozygotes for a G923T substitution in ATP8B1. 1,32 Tissue was fixed in formalin or in buffered glutaraldehyde/paraformaldehyde and was processed through graded ethanols and xylenes, respectively, into paraffin or into resin. Sections of formalin-fixed, paraffin-embedded material cut at 4 m were immunostained and hematoxylin-counterstained, 33 using anti-GGT, 34 anti-CD10 (Novocastra, Newcastle-upon-Tyne, UK), anti-ABCB11, 29 anti-ABCC2 (Signet/Bioquote, York, UK), and anti-ABCB4 (Alexis Biochemicals/Axxora, Nottingham, UK).…”

Clinical utility gene card for: Progressive familial intrahepatic cholestasis type 1

“…Large deletions and genomic rearrangements are also reported (10%). 3,[5][6][7][8] The majority of mutations are 'private' to specific families or ethnic communities. 5 Mutations of ATP8B1 can be found in the NHLBI ESP Exome Variant Server database (http://evs.gs.washington.edu/EVS/).…”

“…7 Benign recurrent intrahepatic cholestasis (BRIC1, OMIM 243300) is also due to biallelic mutations in the ATP8B1 gene but has a less severe phenotype, characterized by intermittent cholestasis without liver scarring. 5 Monoallelic mutation of ATP8B1, predisposes to drug-induced cholestasis (DIC), intrahepatic cholestasis of pregnancy type 1 (ICP1, OMIM 147480) and transient neonatal cholestasis (TNC). 13,14 Specialized medical follow-up should also be offered to heterozygous patients (mainly those who are symptomatic).…”

“…5,7 A chaperone protein, CDC50A, may be required for normal trafficking and function of the product of ATP8B1. 15 No data are available concerning molecular study of the gene encoding CDC50A in patient with a PFIC1 phenotype.…”