title: FIC1 and BSEP defects in Taiwanese patients with chronic intrahepatic cholestasis with low gamma-glutamyltranspeptidase levels.
abstract: To elucidate the frequency of FIC1 (ATP8B1) and BSEP (ABCB11) mutations in Taiwanese children with chronic intrahepatic cholestasis with low gamma-glutamyltranspeptidase (GGT) levels, we assessed 13 unrelated patients with infantile onset chronic intrahepatic cholestasis. Liver complementary DNA sequencing was performed in 7 infants for mutation analyses of FIC1 and BSEP genes. Two distinct liver histologic features were found. Group 1 (n = 5) was characterized by bland cholestasis and group 2 (n = 8) by giant cell transformation. Group 2 patients were associated with higher transaminase levels, alpha-fetoprotein levels, and early mortality. Novel FIC1 mutations were found in all 4 patients tested in group 1, including a 74-bp deletion, a 98-bp deletion, a nonsense, and 2 missense mutations. BSEP mutations were found in 2 of the 3 patients in group 2, including 2 missense mutations and a 1-bp deletion. Phenotypic characterization is useful to differentiate FIC1- from BSEP-related disease.
authors.affiliation: Department of Pediatrics, Pathology, and Clinical Medicine, National Taiwan University Hospital, Taipei.
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Chen
authors.forename: Pei-Shin
authors.initials: PS
authors.lastname: Chang
authors.forename: Hey-Chi
authors.initials: HC
authors.lastname: Hsu
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Ni
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Hsu
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Lee
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Shau
authors.forename: Mei-Hwei
authors.initials: MH
authors.lastname: Chang
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000235:genetics*; D002780:Cholestasis, Intrahepatic / Q000097:blood* / Q000235:genetics*; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D013624:Taiwan; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D005723:gamma-Glutamyltransferase; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human