Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China.
BMC Med Genet. 2019 Jan 18;20(1):18. doi: 10.1186/s12881-019-0753-7.
Progressive familial intrahepatic cholestasis (PFIC) is a group of genetic autosomal recessive disorders that predominantly affects young children and results in early-onset progressive liver damage. Several types of PFIC were defined based on different genetic aetiologies in last decades.
Here, we report a Chinese young child diagnosed as PFIC with variants in tight junction protein 2 (TJP2). The patient was affected by a long history of jaundice, pruritus, and failure to thrive. Highly elevated level of serum total bile acid (TBA) and normal levels of gamma-glutamyltransferase (GGT) were observed at hospitalization. The patient's clinical symptoms could be alleviated by administration of ursodeoxycholic acid. Genetic testing by next generation sequencing (NGS) found novel compound heterozygote mutations c.2448 + 1G > C/c.2639delC (p.T880Sfs*12) in TJP2, which were inherited from her mother and father, respectively. Both mutations were predicted to abolish TJP2 protein translation, and neither has previously been identified.
We report a Chinese female PFIC child with novel compound heterozygous mutations of TJP2. Genetic testing by NGS is valuable in the clinical diagnosis of hereditary liver disease.
进行性家族性肝内胆汁淤积症（PFIC）是一组主要影响幼儿的遗传常染色体隐性疾病，导致早发性进行性肝损伤。在过去几十年中，根据不同的遗传病因，已经定义了几种类型的 PFIC。
在这里，我们报告了一例中国幼儿，其被诊断为具有紧密连接蛋白 2（TJP2）变异的 PFIC。该患者患有长期黄疸、瘙痒和生长不良的病史。住院时观察到血清总胆汁酸（TBA）水平高度升高，γ-谷氨酰转移酶（GGT）水平正常。给予熊去氧胆酸治疗后，患者的临床症状得到缓解。下一代测序（NGS）的基因检测发现 TJP2 中存在新型复合杂合突变 c.2448 + 1G > C/c.2639delC（p.T880Sfs*12），分别从母亲和父亲遗传而来。这两种突变均预测会导致 TJP2 蛋白翻译的终止，且之前均未被识别。
我们报告了一例中国女性 PFIC 患儿，存在 TJP2 的新型复合杂合突变。NGS 基因检测对遗传性肝病的临床诊断具有重要价值。
