未明原因婴儿肝内胆汁淤积症中SLC25A13基因变异特征

目的：了解未明原因婴儿肝内胆汁淤积症中SLC25A13 基因变异特征。方法：收集2016 年1月至2020年12月温州医科大学附属第二医院育英儿童医院儿童消化科住院的未明原因婴儿胆汁淤积症病例，采用二代测序方法筛查SLC25A13 基因变异位点，并进行一代验证，同时加测SLC25A13 两个常见大片段热点变异，然后进行变异特征和功能分析。结果：共收集30例婴儿肝内胆汁淤积症病例，并完成了基因检测。共发现12 例患儿携带SLC25A13 致病性变异位点，该基因在婴儿肝内胆汁淤积症中的检出率高达40%。检出率最高的致病性变异位点为c.852_855delTATG，p.M285Pfs*2，占总检出致病性变异的52.63%（10/19），并发现1个新的致病性变异位点：c.1808T＞C，p.L603P。结论：SLC25A13 基因变异所致Citrin缺陷病是未明原因婴儿肝内胆汁淤积症的重要病因之一，以c.852_855delTATG，p.M285Pfs*2为最常见致病性变异类型。新发现的变异位点扩大了SLC25A13 基因变异谱。

The characteristics of SLC25A13 gene variations of infantile intrahepatic cholestasis with unknown etiology

Objective: To investigate the characteristics of SLC25A13 gene variations of infantile intrahepatic cholestasis with unknown etiology. Methods: Infants with intrahepatic cholestasis of unknown etiology who were hospitalized in the Department of Gastroenterology of the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University from January 2016 to December 2020 were selected. Next generation sequencing was performed to select variations of SLC25A13 gene, and Sanger sequencing was used to identify variations of SLC25A13 gene. Additionally, the two most frequent large- fragment variations of SLC25A13 gene were also detected. Then, the characteristics of SLC25A13 gene variations and its function were analyzed. Results: Genetic testing was performed on 30 infants with intrahepatic cholestasis. SLC25A13 gene pathogenic variants were detected in 12 cases. The frequency of SLC25A13 gene in infantile intrahepatic cholestasis was 40%. The most common variation was c.852_855delTATG, p.M285Pfs*2. A novel variation (c.1808T>C,p.L603P) was identified. Conclusion: Citrin deficiency caused by SLC25A13 gene variation might be the most important cause of infantile intrahepatic cholestasis with unknown etiology, and the c.852_855delTATG,p.M285Pfs*2 was the most common pathogenic variation. The novel variation, which impairs citrin function, has expanded the variation spectrum of SLC25A13 gene.