Objective To explore whether SLC25A13 gene mutation exists and what is its mutation spectrum in mainland Chinese infants with intrahepatic cholestasis and abnormal blood amino acids. Methods Blood amino acids were analyzed by mass chromatographic analysis in infants referred to Fudan University Children's Hospital from June 2003 to June 2007 for investigations of intrahepatic cholestasis of unknown origin. SLC25A13 gene mutations were studied in 14 children whose serum levels of citrulline and/or methionine were at least two times above the upper normal range. In patients in whom only one mutation was detected, all other exons and their neighboring sequences were then analyzed. Results Eight patients with SLC25A13 gene mutations, including 2 with compound heterozygous mutation 851de14/1638ins23, one with homozygous mutation 851de14/851de14, one with compound heterozygous mutation 851de14/R184X, one with homozygous mutation IVS6+1G>A/IVS6+1G>A, and 3 with heterozygous mutation 851de14 were found. Conclusions SLC25A13 gene mutations exist in Chinese infants with intrahepatic cholestasis and abnormal blood amino acids. Their mutation spectrum is different from that in Japan. 851de14 is the most common mutation in our study. IVS6+1G>A is a mutation that has not been reported before.%目的 探讨血氨基酸异常婴儿肝内胆汁淤积症中是否存在SLC25A13基因突变及其突变谱特征.方法 对2003年6月-2007年6月就诊于复旦大学附属儿科医院的不明原因婴儿肝内胆汁淤积症患儿进行血氨基酸质谱分析,将检测有瓜氨酸、蛋氨酸至少一项2倍以上升高者共14例进行基因研究.全部入选对象先行SLC25A13基因的12种突变位点([Ⅰ]851de14、[Ⅱ]IVS11+1G>A、[Ⅲ]1638ins23、[Ⅳ]S225X、[Ⅴ]IVS13+1G>A、[Ⅵ]1800insl、[Ⅶ]R605X、[Ⅷ]E601X、[Ⅸ]E601K、[Ⅹ]IVS6+5G>A、[Ⅺ]R184X及[ⅪⅤ]IVS6+1G>C)的检测.对仅检出单个位点突变的研究对象,继续进行所有外显子区及其邻近序列分析.结果 检出SLC25A13基因突变8例,包括复合杂合突变851de14/1638ins23 2例,纯合突变851de14/851de14、复合杂合突变851de14/R184X及纯合突变IVS6+1G>A/IVS6+1G>各1例,杂合突变851de14 3例,其中纯合突变IVS6+1G>A/IVS6+1G>A是一种新型突变.结论 血氨基酸异常婴儿肝内胆汁淤积症中存在SLC25A13基因突变.[Ⅰ]851de14、[Ⅲ]1638ins23是中国SLC25A13基因的常见突变形式,新发现1例纯合突变IVS6+1G>A/IVS6+1G>A,和国外报道突变谱存在明显区别.
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