广西特发性婴儿肝内胆汁淤积与SLC25A13基因突变

发布时间：2018-04-28 00:33

  本文选题：特发性婴儿肝内胆汁淤积 + SLC25A13基因　； 参考：《广西医科大学》2014年硕士论文

【摘要】：目的：对广西籍特发性婴儿肝内胆汁淤积症患儿进行SLC25A13基因检测，了解其突变情况，并分析疑诊Citrin缺乏性新生儿肝内胆汁淤积症（NICCD）患儿临床表现、实验室检查特点及预后。 方法：收集2011年9月-2013年8月于广西医科大学第一附属医院儿科住院的104例特发性婴儿肝内胆汁淤积的患儿作为病例组，另选取50例肝功能正常的婴儿为对照组。所有研究对象均为广西籍。病例组患儿送检血串联质谱筛查，对疑诊为Citrin缺陷病的患儿直接进行SLC25A13基因全部外显子的DNA测序分析。同时对阴性病例组及对照组采用聚合酶链反应-单链构象多态性（PCR-SSCP）联合DNA测序技术对SLC25A13基因18个外显子进行筛查，了解有无SLC25A13基因突变。并分析疑诊为NICCD的14例患儿的临床表现、实验室检查特点，随访了解其预后。 结果：病例组血串联质谱分析有14例疑诊为Citrin缺陷病，DNA序列直接测序发现SLC25A13基因851del4/851del4纯合突变2例，851del4杂合突变1例,其余串联质谱分析未见异常的病例PCR-SSCP筛查，发现1例第15外显子异常条带，基因测序为SLC25A13基因新型突变P502L。其余对照组并未发现相关突变。串联质谱筛查疑诊为NICCD的14例患儿临床表现为黄疸、不同程度的肝脾肿大，肝功能异常并伴有凝血功能异常，血串联质谱分析显示瓜氨酸、蛋氨酸、酪氨酸升高。其中规律门诊复诊的8例患儿中4例肝功基本恢复正常(其中3例发现SLC25A13基因Ⅰ851del4突变)；1例预后欠佳，3例死亡；余5例均在早期住院治疗不同程度好转出院后失访。 结论:本组特发性婴儿肝内胆汁淤积患儿存在SLC25A13基因突变，SLC25A13基因突变可能是导致本地区婴儿肝内胆汁淤积的主要原因之一；血串联质谱筛查对怀疑Citrin缺乏症的特发性婴儿肝内胆汁淤积症患儿有较高的诊断价值，早期积极接受治疗对于判断预后具有重要意义。
[Abstract]:Objective: to detect the SLC25A13 gene of idiopathic infantile intrahepatic cholestasis in Guangxi and analyze the clinical manifestations, laboratory features and prognosis of Citrin deficiency neonates with intrahepatic cholestasis. Methods: 104 cases of idiopathic infantile intrahepatic cholestasis in pediatrics department of the first affiliated Hospital of Guangxi Medical University from September 2011 to August 2013 were collected as case group and 50 infants with normal liver function as control group. All the subjects are Guangxi nationality. Patients with suspected Citrin deficiency were screened by tandem mass spectrometry, and all exons of SLC25A13 gene were analyzed by DNA sequencing. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) combined with DNA sequencing was used to screen 18 exons of SLC25A13 gene to find out whether there was SLC25A13 gene mutation. The clinical manifestations, laboratory findings and prognosis of 14 children with suspected NICCD were analyzed. Results: there were 14 cases of SLC25A13 homozygous mutation of 851del4/851del4 in 2 cases of homozygous mutation of SLC25A13 gene and 1 case of heterozygous mutation of SLC25A13 gene detected by direct sequencing in 14 cases of suspected Citrin deficiency disease by tandem mass spectrometry analysis. There was no abnormal PCR-SSCP screening in the other cases by tandem mass spectrometry analysis. An abnormal band of exon 15 was found in one case. The gene was sequenced as a new mutation of SLC25A13 gene P502L. No related mutations were found in the other control groups. The clinical manifestations of 14 children with suspected NICCD by tandem mass spectrometry were jaundice, hepatosplenomegaly, abnormal liver function and abnormal coagulation function. Serum tandem mass spectrometry analysis showed that citrulline, methionine and tyrosine were increased. Of the 8 children with regular outpatient visits, 4 had normal liver function (3 of them found that SLC25A13 gene 鈪，

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