The mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and aminoacidemia
The mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and aminoacidemia
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中国婴儿肝内胆汁淤积氨基酸血症SLC25A13基因突变谱
DOI：
10.1007/s00535-010-0329-y
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发表时间：
2011-04-01
影响因子：
6.3
通讯作者：
Wang, Jian-She
中科院分区：
文献类型：
--
作者：
Fu, Hai-Yan;Zhang, Shao-Ren;Wang, Jian-She
研究背景SLC25A13基因突变导致Citrin缺乏症，从而导致Citrin缺乏症引起的新生儿肝内胆汁淤积症（NICCD）。关于中国人群中SLC25A13突变谱的信息有限。本研究的目的是探讨SLC25A13基因突变谱在中国婴儿肝内胆汁淤积症和各种形式的aminoacidemi.MethodsSequence分析39例婴儿肝内胆汁淤积症和各种形式的aminoacidemias.MethodsSequence分析。新的突变进行同源性和结构分析。Western印迹进行时，肝脏标本available.ResultsThe基因检测发现存在SLC25A13基因突变（9杂合子，6纯合子和13复合杂合子）在28名婴儿。随后的Western blot分析显示22例Citrin缺乏症，占39例患者的56.4%。共发现12种突变类型，其中9种为已知突变，3种为新突变（26个等位基因，53.1%），1638ins23 IVS6+5G>A（2个等位基因，4.1%）、E601K（2个等位基因，4.1%）和IVS11+1G>A、R184X、R360X和R585H（各1个等位基因，2.0%）。这三个新的突变是剪接位点的变化（IVS6+1G>A），缺失突变（1092_1095delT）和错义突变（L85 P），每一个在一个allele.ConclusionsThe突变谱的SLC25 A13基因在中国人口的肝内胆汁淤积症与各种形式的氨基酸血症的婴儿被发现是不同的，从其他人口群体在东亚。SLC25A13基因突变是婴儿肝内胆汁淤积症伴各种形式氨基酸血症的最重要原因。
BackgroundSLC25A13 gene mutations cause citrin deficiency, which leads to neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). Information on the mutation spectrum of SLC25A13 in the Chinese population is limited. The aim of this study was to explore the mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and various forms of aminoacidemia.MethodsSequence analyses were performed on 39 infants with intrahepatic cholestasis and various forms of aminoacidemia. Novel mutations were subjected to homology and structural analyses. Western blots were performed when liver specimens available.ResultsGenetic testing revealed the presence of SLC25A13 gene mutations (9 heterozygotes, 6 homozygotes and 13 compound heterozygotes) in 28 infants. Subsequent Western blot analysis revealed 22 cases of citrin deficiency, accounting for 56.4% of the 39 patients. Twelve types of mutations, including nine known mutations and three novel mutations, were found. Of the 49 mutated alleles, known ones include 851del4 (26 alleles, 53.1%), 1638ins23 (6 alleles, 12.2%), IVSl6ins3kb (3 alleles, 6.1%), IVS6+5G>A (2 alleles, 4.1%), E601K (2 alleles, 4.1%) and IVS11+1G>A, R184X, R360X and R585H (1 allele each, 2.0%). The three novel mutations were a splice site change (IVS6+1G>A), a deletion mutation (1092_1095delT) and a missense mutation (L85P), each in one allele.ConclusionsThe mutation spectrum of the SLC25A13 gene in a Chinese population of infants with intrahepatic cholestasis with various forms of aminoacidemia was found to be different from that of other population groups in East Asia. The SLC25A13 gene mutation is the most important cause of infantile intrahepatic cholestasis with various forms of aminoacidemia.