五例新生儿肝内胆汁淤积症患儿SLC25A13基因的突变分析

Analysis of SLC25AI3 gene mutations in five infants with neonatal intrahepatic cholestasis caused by citrin deficiency

目的明确5例新生儿肝内胆汁淤积症患儿的分子机制。方法应用新一代测序技术对患儿的5LC25A13基因进行外显子捕获检测，对突变位点进行Sanger测序验证。用PolyPhen-2软件对新突变的致病性进行分析。结果5例患儿均携带SLC25A13基因的复合突变，共发现8个突变位点，其中2个既往未见报道（C．1357A^G和C．1663dup23）。5例患儿的父母均为突变携带者。结论SLC25A13基因的突变可能是5例患儿的发病原因，所携带的突变以851de14和16381660dup为主。新发现的c．1357A〉G和C．1663dup23突变丰富了SI．C25A13基因的突变谱。

Objective To identify potential mutations in five infants with neonatal intrahepatic cholestasis caused by eitrin deficiency （NICCD）. Methods The SLC25A13 gene was analyzed by next generation sequencing. Suspected mutations were confirmed by PCR and Sanger sequencing in the probands and their parents. Impact of novel mutations was predicted with PolyPhen-2 software. Results All neonates have harbored mutations of the SLC25A13 gene. Eight mutations were discovered, which included two novel mutations （c. 1357A〉G and c. 1663dup23）. All parents were found to be carriers of the mutations. Conclusion Mutations of the SLC25A13 gene probably underlie the NICCD among the five patients, among which 851de14 and 1638-1660dup were the most common ones. This has enriched the spectrum of SLC25A13 mutation in association with NICCD.