【作者】 高国鹏；

【导师】 王琳琳；

【作者基本信息】 广西医科大学 ， 儿科学， 2012， 硕士

【摘要】 目的：对特发性婴儿肝炎肝内胆汁淤积患儿的BSEP基因进行筛查,初步探讨胆盐输出泵基因与特发性婴儿肝炎肝内胆汁淤积的关系。方法：收集2009年10月至2011年02月于广西医科大学第一附属医院儿科住院的特发性婴儿肝炎肝内胆汁淤积的患儿115例作为病例组,60例无胆汁淤积婴儿作为对照组,应用聚合酶链反应-单链构象多态性分析(PCR-SSCP)方法对BSEP基因上的7、8、11、12、14、15、18、21、26外显子进行检测。对有异常条带的外显子进行测序,结果在Genbank基因库上进行序列比较。结果：在2例患儿BSEP基因的第7外显子上检测到相同未报道的杂合突变c.499G>T,导致基因编码的BSEP蛋白的第167位丙氨酸(Ala)被丝氨酸(Ser)所替代(p.A167S)。该位点的突变未在其余病人与对照组中检测出。结论：本研究在特发性婴儿肝炎胆汁淤积患儿的BSEP基因第7外显子上发现一个新的错义突变A167S。A167S可能在婴儿特发性肝炎肝内胆汁淤积的发生机制中发挥一定的作用,并可能对突变相关类型的肝内胆汁淤积的预后有一定的指导意义。更多还原

【Abstract】 Objective:To screen the BSEP gene in intrahepatic cholestasis of idiopathic infantile hepatitis patients. And investigate the relationship between intrahepatic cholestasis of idiopathic infantile hepatitis and bile salt export pump gene.Methods:A total of115cases of idiopathic infantile hepatitis with intrahepatic cholestasis in case group and60idiopathic infantile hepatitis persons who had no intrahepatic cholestasis in the control group were collected in paediatrics department of the First Affiliated Hospital of Guangxi Medical University from Oct.2009to Feb.2011. The exons of BSEP gene7,8,11,12,14,15,18,21were screening by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), The PCR products which had abnormal bands in SSCP were sequenced by DNA sequencer. The sequenced results were comared with the normal gen in the Genbank database.Results:Two new cases of heterozygous mutation c.499G>T were detected in the exon7of BSEP gene. This mutation caused genetic code of BSEP protein167th alanine (Ala) be serine (Ser) replacement (p.A167S). There were not mutation found in the other patients and the control group. Conclusions:A167S is a heterozygous nonsense mutation in exon7of BSEP. Which show that A167S maybe play an important role in cholestasis in idiopathic infantile hepatitis and it will give some useful information for the prognosis of cholestasis in the future.更多还原