1例进行性家族性肝内胆汁淤积症2型婴儿的临床和遗传学分析

Clinical and genetic analysis of an infant with progressive familial intrahepatic cholestasis type II

摘要:

进行性家族性肝内胆汁淤积症2型（PFIC-2）是ABCB11基因突变引起的常染色体隐性遗传病。本文报道1例PFIC-2患儿的临床及实验室特征。患儿，男，2.4个月，主要表现为黄疸、肝肿大，以及血清总胆红素、结合胆红素和总胆汁酸明显升高，但γ-谷氨酰转肽酶（GGT）正常。二代测序（NGS）发现患儿ABCB11基因存在两个错义变异：c.1493T > C（p.Ile498Thr）和c.1502T > G（p.Val501Gly），分别来自其父母。前者为文献报道的致病性变异；c.1502T > G为未见报道的新变异类型，受累氨基酸在112个物种同源肽中高度保守，经多种生物信息学工具预测变异具有致病性。

Abstract:

Progressive familial intrahepatic cholestasis type Ⅱ (PFIC-2) is an autosomal recessive disorder caused by biallelic variants of ABCB11 gene. This paper reports the clinical and laboratory features of a pediatric patient with PFIC-2. The patient was a 2.4-month-old male infant with jaundice and hepatomegaly as the main clinical manifestations. The serum levels of total bilirubin, direct bilirubin and total bile acids were increased, while the serum γ-glutamyl transpeptidase (GGT) level was normal. Next generation sequencing revealed two missense variants, c.1493T > C(p.Ile498Thr) and c.1502T > G(p.Val501Gly), in the ABCB11 gene of the patient, which were inherited from his father and mother, respectively. The latter was a novel variant which was predicted to be pathogenic by using a variety of bioinformatic tools, and the affected p.Val501 residue was highly conserved in 112 homologous peptides.