Chen Huey-Ling, Chang Pei-Shin, Hsu Hey-Chi, Ni Yen-Hsuan, Hsu Hong-Yuan, Lee Jyh-Hong, Jeng Yung-Ming, Shau Wen-Yi, Chang Mei-Hwei
Department of Pediatrics, Pathology, and Clinical Medicine, National Taiwan University Hospital, Taipei.
J Pediatr. 2002 Jan;140(1):119-24. doi: 10.1067/mpd.2002.119993.
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.
为了阐明台湾地区慢性肝内胆汁淤积伴低γ-谷氨酰转肽酶（GGT）水平儿童中FIC1（ATP8B1）和BSEP（ABCB11）突变的频率，我们评估了13例无关的婴儿期起病的慢性肝内胆汁淤积患者。对7例婴儿进行了肝脏互补DNA测序，以分析FIC1和BSEP基因的突变情况。发现了两种不同的肝脏组织学特征。第1组（n = 5）的特征为单纯性胆汁淤积，第2组（n = 8）的特征为巨细胞转化。第2组患者的转氨酶水平、甲胎蛋白水平较高，且早期死亡率较高。在第1组检测的所有4例患者中均发现了新的FIC1突变，包括一个74 bp的缺失、一个98 bp的缺失、一个无义突变和2个错义突变。在第2组的3例患者中有2例发现了BSEP突变，包括2个错义突变和一个1 bp的缺失。表型特征有助于区分FIC1相关疾病和BSEP相关疾病。
