Bai Jie, Li Lu, Liu Hui, Liu Shuang, Bai Li, Ning Hanbing, Song Wenyan, Zou Huaibin, Wang Xinxin, Chen Yu, Zheng Sujun, Duan Zhongping
Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You An Hospital, Capital Medical University, Beijing, China.
Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China.
Ann Transl Med. 2021 Mar;9(5):426. doi: 10.21037/atm-20-3747.
Progressive familial intrahepatic cholestasis (PFIC) includes a group of genetic autosomal recessive disorders that predominantly affects young children and results in early-onset progressive liver damage. Variations in have been shown to cause PFIC3. However, the association between genotype and clinical manifestations remains unclear. We investigated the clinical manifestations and genetic features of a Chinese Han pedigree with PFIC3. A 15-year-old boy, with high-serum gamma-glutamyl transferase (γ-GT) cholestatic cirrhosis, was diagnosed with PIFC3. After ursodeoxycholic acid (UDCA) treatment, the boy stayed in a relatively stable state with mild itching, and elevated γ-GT exhibited a remarkable decrease. Genetic testing identified a novel compound heterozygous mutation L842P/V1051A in , which was inherited from his mother and father, respectively. Several predictive software suggested that these two mutations are pathogenic. Interestingly, the same compound heterozygous mutation was also found in his two sisters, one of whom had a history of intrahepatic cholestasis of pregnancy (ICP) and the other had asymptomatic gallstones. Therefore, this novel compound heterozygous mutation L842P/V1051A caused a continuum of -related diseases including ICP, cholelithiasis and PFIC3 in our pedigree. The inconsistency between genotypes and phenotypes may be influenced by other factors. Genetic testing will be useful for diagnosis and genetic counseling.
进行性家族性肝内胆汁淤积症（PFIC）包括一组常染色体隐性遗传疾病，主要影响幼儿，并导致早发性进行性肝损伤。已证明[相关基因]的变异会导致PFIC3。然而，[相关基因]基因型与临床表现之间的关联仍不清楚。我们调查了一个患有PFIC3的中国汉族家系的临床表现和遗传特征。一名15岁男孩，患有高血清γ-谷氨酰转移酶（γ-GT）胆汁淤积性肝硬化，被诊断为PIFC3。经熊去氧胆酸（UDCA）治疗后，该男孩病情相对稳定，有轻度瘙痒，γ-GT升高显著下降。基因检测在[相关基因]中鉴定出一种新的复合杂合突变L842P/V1051A，分别从他的母亲和父亲遗传而来。几种预测软件表明这两个突变具有致病性。有趣的是，在他的两个姐妹中也发现了相同的复合杂合突变，其中一个有妊娠期肝内胆汁淤积症（ICP）病史，另一个有无症状胆结石。因此，这种新的复合杂合突变L842P/V1051A在我们的家系中导致了一系列与[相关基因]相关的疾病，包括ICP、胆石症和PFIC3。基因型与表型之间的不一致可能受其他因素影响。基因检测将有助于诊断和遗传咨询。
