The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China.
Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, China.
Pediatr Res. 2020 Jan;87(1):112-117. doi: 10.1038/s41390-019-0548-8. Epub 2019 Aug 26.
Genetic defects account for a substantial proportion of pediatric cholestasis. This study explored the molecular findings in a large cohort of Chinese patients with inherited cholestasis.
Between January 2012 and June 2016, 809 Chinese pediatric patients with suspected inherited intrahepatic cholestasis were evaluated by Sanger sequencing and/or panel sequencing.
Of the 809 patients, 273 (33.7%) obtained a genetic diagnosis. The rate of positive genetic diagnosis in patients with disease onset at 0-3 month of age was higher than that in patients with disease onset at 4 month of age or later. There were 17 distinct genetic defects diagnosed. The top 4 resulted from mutations in SLC25A13 (44.3%), JAG1 (24.5%), ABCB11 (11.0%), and ATP8B1 (5.9%). All 17 genetic disorders were diagnosed in patients with disease onset at 0-3 months of age; but only 5 were diagnosed in patients with disease onset beyond 4 months of age. A total of 217 distinct pathogenic variants, including 41 novel variants, were identified. Ten recurrent mutations were detected in SLC25A13, ATP8B1, and CYP27A1. They accounted for 48.2% of the total 477 mutant alleles.
There were 17 distinct genetic disorders diagnosed in Chinese pediatric patients with inherited cholestasis.
遗传缺陷在小儿胆汁淤积症中占很大比例。本研究探讨了中国一大组遗传性胆汁淤积症患者的分子发现。
2012 年 1 月至 2016 年 6 月，对 809 例疑似遗传性肝内胆汁淤积的中国儿科患者进行 Sanger 测序和/或面板测序。
809 例患者中，273 例（33.7%）获得遗传诊断。发病年龄在 0-3 个月的患者阳性遗传诊断率高于发病年龄在 4 个月或以上的患者。共诊断出 17 种不同的遗传缺陷。前 4 种是由 SLC25A13（44.3%）、JAG1（24.5%）、ABCB11（11.0%）和 ATP8B1（5.9%）突变引起的。所有 17 种遗传疾病均在发病年龄在 0-3 个月的患者中确诊；但只有 5 种在发病年龄在 4 个月以上的患者中确诊。共发现 217 种不同的致病性变异，包括 41 种新变异。在 SLC25A13、ATP8B1 和 CYP27A1 中检测到 10 个高频突变。它们占 477 个突变等位基因的 48.2%。
在中国遗传性胆汁淤积症的儿科患者中，共诊断出 17 种不同的遗传疾病。
