直接胆红素增高的黄疸患儿SLC25A13基因热点突变分析

SLC25A13 gene hotspot mutation analysis in direct bilirubin elevated jaundice patients

目的建立快速诊断citrin缺陷导致的新生儿肝内胆汁淤积症(NICCD)的方法,初步探讨NICCD在直接胆红素增高的黄疸患儿中所占比例。方法应用聚合酶链反应(PCR)和聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)对122例表现为直接胆红素增高的黄疸患儿SLC25A13基因(热点突变分析位点包括:851del4、1638ins23、IVS6+5G>A、IVS16ins3kb和IVS11+1G>A)进行热点突变分析。结果在122例纳入实验研究的患者中,发现6例患儿为851del4纯合子;2例为1638ins23/IVS6+5G>A突变;2例为851del4/IVS16ins3kb突变。还有8例患儿只发现了一个SLC25A13基因突变,其相应等位突变尚不清楚,但是后续的实验证实了这8例患儿为NICCD。暂时未发现有IVS11+1G>A突变。在这些热点突变类型中以851del4突变所占比例最高,占了71.4%(20/28),其次为IVS16ins3kb和1638ins23,各占10.7%。NICCD患儿占总受检人数的14.7%。结论 1.SLC25A13基因热点突变分析能快速准确地诊断NICCD。2.SLC25A13基因突变以851del最为常见。3.NICCD在直接胆红素增高的黄疸患儿中占相当高的比例。

Objective：To diagnosis the neonatal intrahepatic cholestasis caused by citrin deficiency（NICCD） in direct bilirubin elevated jaundice patients,quick test were established.Methods：Applied PCR and PCR-RFLP to analyze SLC25A13 gene hotspot mutation,including 851del4,1638ins23,IVS6＋5GA,IVS16ins3kb and IVS11＋1GA,in 122 direct bilirubin elevated jaundice patients.Results：In the present study,we found that six patients were 851del4 homozygotes,two patients were 1638ins23/IVS6＋5GA heterozygotes and two patients were 851del4/IVS16ins3kb heterozygotes.Eight patients were just found one alleles mutation,but the follow up experiment proved those eight patients were NICCD.IVS11＋1GA mutation were not detected.In all hotspot mutation types,851del have the most high rate,accounted for 71.4%（20/28）.And the next were IVS16ins3kb and 1638ins23,which accounted for 10.7%.Conclusion：1.SLC25A13 gene hotspot mutation analysis can identify NICCD rapidly.2.851del4 is the most common mutation type.3.In direct bilirubin evaluated jaundice patients,NICCD have a very high incidence rate.