z-logo
Premium
Characterization of mutations in ATP8B1 associated with hereditary cholestasis
Author(s) -
Klomp Leo W. J.,
Vargas Julie C.,
van Mil Saskia W. C.,
Pawlikowska Ludmila,
Strautnieks Sandra S.,
van Eijk Michiel J. T.,
Juijn Jenneke A.,
PabónPeña Carlos,
Smith Lauren B.,
DeYoung Joseph A.,
Byrne Jane A.,
Gombert Justijn,
van der Brugge Gerda,
Berger Ruud,
Jankowska Irena,
Pawlowska Joanna,
Villa Erica,
Knisely A. S.,
Thompson Richard J.,
Freimer Nelson B.,
Houwen Roderick H. J.,
Bull Laura N.
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20285
Subject(s) - cholestasis , genetics , mutation , biology , medicine , computational biology , gene
Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are clinically distinct hereditary disorders. PFIC patients suffer from chronic cholestasis and develop liver fibrosis. BRIC patients experience intermittent attacks of cholestasis that resolve spontaneously. Mutations in ATP8B1 (previously FIC1) may result in PFIC or BRIC. We report the genomic organization of ATP8B1 and mutation analyses of 180 families with PFIC or BRIC that identified 54 distinct disease mutations, including 10 mutations predicted to disrupt splicing, 6 nonsense mutations, 11 small insertion or deletion mutations predicted to induce frameshifts, 1 large genomic deletion, 2 small inframe deletions, and 24 missense mutations. Most mutations are rare, occurring in 1-3 families, or are limited to specific populations. Many patients are compound heterozygous for 2 mutations. Mutation type or location correlates overall with clinical severity: missense mutations are more common in BRIC (58% vs. 38% in PFIC), while nonsense, frameshifting, and large deletion mutations are more common in PFIC (41% vs. 16% in BRIC). Some mutations, however, lead to a wide range of phenotypes, from PFIC to BRIC or even no clinical disease. ATP8B1 mutations were detected in 30% and 41%, respectively, of the PFIC and BRIC patients screened.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here