發(fā)布時(shí)間：2018-04-28 00:33

  本文選題：特發(fā)性嬰兒肝內(nèi)膽汁淤積 + SLC25A13基因��； 參考：《廣西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：對(duì)廣西籍特發(fā)性嬰兒肝內(nèi)膽汁淤積癥患兒進(jìn)行SLC25A13基因檢測(cè)，了解其突變情況，并分析疑診Citrin缺乏性新生兒肝內(nèi)膽汁淤積癥（NICCD）患兒臨床表現(xiàn)、實(shí)驗(yàn)室檢查特點(diǎn)及預(yù)后。 方法：收集2011年9月-2013年8月于廣西醫(yī)科大學(xué)第一附屬醫(yī)院兒科住院的104例特發(fā)性嬰兒肝內(nèi)膽汁淤積的患兒作為病例組，另選取50例肝功能正常的嬰兒為對(duì)照組。所有研究對(duì)象均為廣西籍。病例組患兒送檢血串聯(lián)質(zhì)譜篩查，對(duì)疑診為Citrin缺陷病的患兒直接進(jìn)行SLC25A13基因全部外顯子的DNA測(cè)序分析。同時(shí)對(duì)陰性病例組及對(duì)照組采用聚合酶鏈反應(yīng)-單鏈構(gòu)象多態(tài)性（PCR-SSCP）聯(lián)合DNA測(cè)序技術(shù)對(duì)SLC25A13基因18個(gè)外顯子進(jìn)行篩查，了解有無(wú)SLC25A13基因突變。并分析疑診為NICCD的14例患兒的臨床表現(xiàn)、實(shí)驗(yàn)室檢查特點(diǎn)，隨訪了解其預(yù)后。 結(jié)果：病例組血串聯(lián)質(zhì)譜分析有14例疑診為Citrin缺陷病，DNA序列直接測(cè)序發(fā)現(xiàn)SLC25A13基因851del4/851del4純合突變2例，851del4雜合突變1例,其余串聯(lián)質(zhì)譜分析未見(jiàn)異常的病例PCR-SSCP篩查，發(fā)現(xiàn)1例第15外顯子異常條帶，基因測(cè)序?yàn)镾LC25A13基因新型突變P502L。其余對(duì)照組并未發(fā)現(xiàn)相關(guān)突變。串聯(lián)質(zhì)譜篩查疑診為NICCD的14例患兒臨床表現(xiàn)為黃疸、不同程度的肝脾腫大，肝功能異常并伴有凝血功能異常，血串聯(lián)質(zhì)譜分析顯示瓜氨酸、蛋氨酸、酪氨酸升高。其中規(guī)律門(mén)診復(fù)診的8例患兒中4例肝功基本恢復(fù)正常(其中3例發(fā)現(xiàn)SLC25A13基因Ⅰ851del4突變)；1例預(yù)后欠佳，3例死亡；余5例均在早期住院治療不同程度好轉(zhuǎn)出院后失訪。 結(jié)論:本組特發(fā)性嬰兒肝內(nèi)膽汁淤積患兒存在SLC25A13基因突變，SLC25A13基因突變可能是導(dǎo)致本地區(qū)嬰兒肝內(nèi)膽汁淤積的主要原因之一；血串聯(lián)質(zhì)譜篩查對(duì)懷疑Citrin缺乏癥的特發(fā)性嬰兒肝內(nèi)膽汁淤積癥患兒有較高的診斷價(jià)值，早期積極接受治療對(duì)于判斷預(yù)后具有重要意義。
[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，

本文編號(hào)：1813009