FIC1 and BSEP defects in Taiwanese patients with chronic intrahepatic cholestasis with low gamma-glutamyltranspeptidase levels.
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.
Chen
Huey-Ling
HL
Department of Pediatrics, Pathology, and Clinical Medicine, National Taiwan University Hospital, Taipei.
Chang
Pei-Shin
PS
Hsu
Hey-Chi
HC
Ni
Yen-Hsuan
YH
Hsu
Hong-Yuan
HY
Lee
Jyh-Hong
JH
Jeng
Yung-Ming
YM
Shau
Wen-Yi
WY
Chang
Mei-Hwei
MH
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*
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