Abstract: Objective To investigate genetic features of SLC25A13 gene with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). Methods Genomic DNA was extracted from peripheral blood leukocytes in 42 patients with idiopathic cholestasis.Polymerase chain reaction,direct sequencing and genetic analysis were performed using specific primers from 18 exons of SLC25A13 gene. Results 7 patients were diagnosed with NICCD,of which two patients were homozygous 851del4 mutation:c.851_854delGTAT (p.Met284fs) / c.851_854delGTAT (p.Met284fs).Other five patients were compound heterozygous mutations:c.851_854delGTAT (p.Met284fs) / c.754G>A (p.Glu252Lys);g.IVS11+1G>A /g.IVS16ins3kb;c.851_854delGTAT (p.Met284fs) / g.IVS6+5G>A; c.G1064G>A (p.Arg355Gln) / c.G1157G>T (p.Gly386Val); c.1078C>T (p.Arg360Term) / c.IVS4+6A>G. Conclusion c.851_854delGTAT (p.Met284fs) are detected in 6 out of 14 SLC25A13 gene mutant alleles,with a mutation rate of 42.8% (6/14) in 7 patients with NICCD.It is the major mutation (42.8%) in SLC25A13 gene with NICCD patients.Genetic analysis for SLC25A13 gene are helpful to the diagnoses of NICCD.   

Key words: SLC25A13 gene, neonatal intrahepatic cholestasis, citrin deficiency

摘要： 目的 分析citrin 缺陷导致的新生儿肝内胆汁淤积症(NICCD)患儿SLC25A13基因突变特点。方法 抽取42例胆汁淤积性肝病患儿血液DNA,应用PCR 扩增和测序进行SLC25A13 基因突变分析。结果 7例患儿诊断为NICCD,其中2例患儿为纯合突变,均为c.851_854delGTAT(p.Met284fs)/c.851_854delGTAT(p.Met284fs);其它5 例患儿为复合杂合突变,分别为c.851_854delGTAT(p.Met284fs)/c.754G>A(p.Glu252Lys);g.IVS11+1G>A /g.IVS16ins3kb; c.851_854delGTAT(p.Met284fs)/g.IVS6+5G>A;c.G1064G>A(p.Arg355Gln)/c.G1157G>T (p.Gly386Val);c.1078C>T(p.Arg360Term)/c.IVS4+6A>G。结论 7例患儿的14个突变单链中,6个单链发生c.851_854delGTAT(p.Met284fs)突变,其在14个突变单链中的比率为42.8%(6/14),c.851_854delGTAT(p.Met284fs)为本组SLC25A13 基因主要突变(42.8%)类型,基因检测分析有助于NICCD 的诊断。

关键词: SLC25A13基因, 新生儿肝内胆汁淤积症, citrin缺陷