Center for Pediatric Liver Diseases, Children's Hospital of Fudan University; Department of Pediatrics, Shanghai Medical College of Fudan University, 399 Wanyuan Road, Minhang, Shanghai, China.
J Pediatr Gastroenterol Nutr. 2010 Feb;50(2):179-83. doi: 10.1097/MPG.0b013e3181c1b368.
The aim of the study was to elucidate the role and characteristics of ATP8B1 gene mutations in mainland Chinese children with progressive intrahepatic cholestasis and low gamma-glutamyltransferase (GGT).
Twenty-four children who presented with progressive intrahepatic cholestasis and low GGT were admitted to a tertiary pediatric hospital in eastern China from January 2004 to July 2007. Five children with homozygous or compound heterozygous ABCB11 gene mutations were excluded from the study. All encoding exons and their flanking areas of ATP8B1 gene were sequenced in the remaining 19 patients, in whom only 1 or no mutation of ABCB11 was found. Clinical features and liver histology obtained by reviewing the medical records were compared among patients with different genotypes.
Nine mutations of ATP8B1 gene were found in 9 patients. All of them were novel except for mutations I694N and R952X. A linked P209T and IVS6+5G>T mutation was found in 4 of 9 patients, including 2 homozygotes and 2 heterozygotes. Giant cell transformation of hepatocytes was demonstrated in 1 of 6 patients with ATP8B1 mutations and 4 of 5 patients with ABCB11 mutations.
ATP8B1 gene mutations play an important role in Chinese patients with progressive intrahepatic cholestasis and low GGT. The linked mutation P209T and IVS6+5G>T is a hot mutation in the Chinese population. Histological examination may be helpful in differentiating familial intrahepatic cholestasis type 1 from bile salt export pump-related disease.
本研究旨在阐明 ATP8B1 基因突变在中国大陆患有进行性肝内胆汁淤积症和低 γ-谷氨酰转肽酶（GGT）的儿童中的作用和特征。
2004 年 1 月至 2007 年 7 月，中国东部一家三级儿科医院收治了 24 例患有进行性肝内胆汁淤积症和低 GGT 的儿童。排除了 5 例具有 ABCB11 基因纯合或复合杂合突变的儿童。在其余 19 例患者中，仅发现 1 种或 1 种以上 ABCB11 基因突变，对其 ATP8B1 基因所有编码外显子及其侧翼区域进行测序。通过查阅病历比较不同基因型患者的临床特征和肝组织学表现。
在 9 例患者中发现了 9 种 ATP8B1 基因突变。除 I694N 和 R952X 突变外，均为新突变。在 9 例患者中发现了 4 例 P209T 和 IVS6+5G>T 的连锁突变，包括 2 例纯合子和 2 例杂合子。在 6 例 ATP8B1 基因突变患者中有 1 例和在 5 例 ABCB11 基因突变患者中有 4 例观察到肝细胞巨细胞转化。
ATP8B1 基因突变在中国大陆患有进行性肝内胆汁淤积症和低 GGT 的患者中起重要作用。连锁突变 P209T 和 IVS6+5G>T 是中国人群中的热点突变。组织学检查有助于区分 1 型家族性肝内胆汁淤积症和胆盐输出泵相关疾病。
