特发性婴儿肝内胆汁淤积症患儿SLC25A13基因突变分析

SLC25A13 gene mutation screening in infants with intrahepatic cholestasis

目的探讨特发性婴儿肝内胆汁淤积症患儿SLC25A13基因的突变情况。方法收集特发性婴儿肝内胆汁淤积症患儿95例作为病例组,另取50例无肝内胆汁淤积、肝功能正常的婴儿作为对照组。所有研究对象全为广西籍。病例组患儿送检血氨基酸质谱分析筛查,对筛查怀疑为Citrin缺乏症的7例全部行DNA测序分析。同时提取病例组其他患儿和对照组婴儿外周血DNA,采用聚合酶链反应-单链构象多态性和DNA测序技术检测SLC25A13基因上18个外显子基因,分析SLC25A13基因突变及突变类型。结果共检出SLC25A13基因突变4例。伴有瓜氨酸、蛋氨酸升高检出3例,包括851del4/851del4纯合突变2例,851del4杂合突变1例;不伴有瓜氨酸、蛋氨酸升高的新型突变P502L 1例。结论广西特发性婴儿肝内胆汁淤积症患儿SLC25A13基因存在851del4/851del4纯合突变,851del4杂合突变;并在不伴有血氨基酸质谱异常的患儿中发现国外未曾报道的新型突变P502L。

Objective To evaluate the SLC25A13 gene mutation in the pathogenesis of infants with intrahepatic cholestasis.Methods The genomic DNA was obtained from peripheral blood of 95 infants with intrahepatic cholestasis , who hospitalized in the department of pediatrics of the first affiliated hospital of Guangxi medical university from Oct .2011 to Mar.2012, as case group.Case group diagnosis was proven by blood amino acid mass chromatography analysis , and suspected citrin deficiency children were further proved with direct gene sequencing analysis .Fifty normal liver function infants without intrahepatic cholestasis were selected as control group .All exons of SLC25A13 gene were genotyped by polymerase chain reaction single strand conformation polymorphism （PCR-SSCP） and DNA sequenced.The correlation between the SLC25A13 gene and intrahepatic cholestasis in infants was analyzed .Results SLC25A13 gene mutation was found 4 patients;among whom 3 patients were found with abnormal blood amino acid mass chromatography , including 2 patients with homozygous mutation 851del4/851del4 and 1 patient with heterozygous mutation 851del4.Conclusion Homozygous mutation 851del4/851del4 and heterozygous mutation 851del4 in SLC25A13 gene are revealed in infants with intrahepatic cholestasis from Guangxi .A new mutation type P502L in patients without abnormal blood amino acid mass chromatography analysis was reported .