Fang Youhong, Yu Jindan, Lou Jingan, Peng Kerong, Zhao Hong, Chen Jie
National Clinical Research Center for Child Health, Department of Gastroenterology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Pediatr. 2021 Mar 4;9:631620. doi: 10.3389/fped.2021.631620. eCollection 2021.
Children presenting with chronic liver disease or acute liver failure often have an underlying genetic disorder. The aim of this study was to analyze the clinical and genetic spectra of inherited liver disease in children in a tertiary hospital. A total of 172 patients were classified into three groups according to their clinical presentation: cholestasis (Group A), liver enzyme elevation (Group B), and hepato/splenomegaly (Group C). Next-generation sequencing (NGS) was performed on all patients recruited in this study. The genotypic and phenotypic spectra of disease in these patients were reviewed. The median age at enrollment of the 172 patients was 12.0 months (IQR: 4.9, 42.5 months), with 52.3% males and 47.7% females. The overall diagnostic rate was 55.8% (96/172) in this group. The diagnostic rates of whole-exome sequencing (WES) and targeted gene panel sequencing (TGPS) were 47.2% and 62.0%, respectively (no significant difference, = 0.054). We identified 25 genes related to different phenotypes, including 46 novel disease-related pathogenic mutations. The diagnostic rates in the three groups were 46.0% (29/63), 48.6% (34/70), and 84.6% (33/39). , and were the top three genes related to monogenic liver disease in this study. WES and TGPS show similar diagnostic rates in the diagnosis of monogenic liver disease. NGS has an important role in the diagnosis of monogenetic liver disease and can provide more precise medical treatment and predict the prognosis of these diseases.
患有慢性肝病或急性肝衰竭的儿童往往存在潜在的遗传疾病。本研究的目的是分析一家三级医院中儿童遗传性肝病的临床和基因谱。根据临床表现，共172例患者被分为三组：胆汁淤积组（A组）、肝酶升高组（B组）和肝脾肿大组（C组）。对本研究纳入的所有患者进行了二代测序（NGS）。回顾了这些患者疾病的基因型和表型谱。172例患者的中位入组年龄为12.0个月（四分位间距：4.9，42.5个月），男性占52.3%，女性占47.7%。该组的总体诊断率为55.8%（96/172）。全外显子组测序（WES）和靶向基因panel测序（TGPS）的诊断率分别为47.2%和62.0%（无显著差异，P = 0.054）。我们鉴定出25个与不同表型相关的基因，包括46个新的疾病相关致病突变。三组的诊断率分别为46.0%（29/63）、48.6%（34/70）和84.6%（33/39）。 、 和 是本研究中与单基因肝病相关的前三个基因。WES和TGPS在单基因肝病诊断中显示出相似的诊断率。NGS在单基因肝病诊断中具有重要作用，可为这些疾病提供更精确的治疗并预测预后。
