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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 胡務亮(Wuh-Liang Hwu) | |
dc.contributor.author | Li-Yun Wang | en |
dc.contributor.author | 王里勻 | zh_TW |
dc.date.accessioned | 2021-06-15T05:42:57Z | - |
dc.date.available | 2012-10-05 | |
dc.date.copyright | 2011-10-05 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-19 | |
dc.identifier.citation | 1. Chace, D. H. and W. H. Hannon 'Impact of second-tier testing on the effectiveness of newborn screening.' Clin Chem 56(11): 1653-5.
2. Chang, K. W., H. L. Chen, et al. 'SLC25A13 gene mutations in Taiwanese patients with non-viral hepatocellular carcinoma.' Mol Genet Metab 103(3): 293-6. 3. Chen, H. W., H. L. Chen, et al. (2008). 'Chubby face and the biochemical parameters for the early diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency.' J Pediatr Gastroenterol Nutr 47(2): 187-92. 4. Hwu, W. L., K. Kobayashi, et al. (2001). 'A Chinese adult onset type II citrullinaemia patient with 851del4/1638ins23 mutations in the SLC25A13 gene.' J Med Genet 38(7): E23. 5. Iijima, M., A. Jalil, et al. (2001). 'Pathogenesis of adult-onset type II citrullinemia caused by deficiency of citrin, a mitochondrial solute carrier protein: tissue and subcellular localization of citrin.' Adv Enzyme Regul 41: 325-42. 6. Ikeda, S., M. Yazaki, et al. (2001). 'Type II (adult onset) citrullinaemia: clinical pictures and the therapeutic effect of liver transplantation.' J Neurol Neurosurg Psychiatry 71(5): 663-70. 7. Imamura, Y., K. Kobayashi, et al. (2003). 'Effectiveness of carbohydrate-restricted diet and arginine granules therapy for adult-onset type II citrullinemia: a case report of siblings showing homozygous SLC25A13 mutation with and without the disease.' Hepatol Res 26(1): 68-72. 8. Ko, J. M., G. H. Kim, et al. (2007). 'Six cases of citrin deficiency in Korea.' Int J Mol Med 20(6): 809-15. 9. Ko, J. S., J. H. Song, et al. (2007). 'Neonatal intrahepatic cholestasis caused by citrin deficiency in Korean infants.' J Korean Med Sci 22(6): 952-6. 10. Kobayashi, K., Y. Bang Lu, et al. (2003). 'Screening of nine SLC25A13 mutations: their frequency in patients with citrin deficiency and high carrier rates in Asian populations.' Mol Genet Metab 80(3): 356-9. 11. Kobayashi, K. and T. Saheki (1993). 'Citrin Deficiency.' 12. Kobayashi, K. and T. Saheki (2004). '[Molecular basis of citrin deficiency].' Seikagaku 76(12): 1543-59. 13. Komatsu, M., M. Yazaki, et al. (2008). 'Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease.' J Hepatol 49(5): 810-20. 14. Lee, N. C., Y. H. Chien, et al. (2006). 'Time course of acylcarnitine elevation in neonatal intrahepatic cholestasis caused by citrin deficiency.' J Inherit Metab Dis 29(4): 551-5. 15. Lin, J. T., K. J. Hsiao, et al. 'High resolution melting analysis for the detection of SLC25A13 gene mutations in Taiwan.' Clin Chim Acta 412(5-6): 460-5. 16. Lu, Y. B., K. Kobayashi, et al. (2005). 'Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency.' J Hum Genet 50(7): 338-46. 17. Naito, E., M. Ito, et al. (2002). 'Type II citrullinaemia (citrin deficiency) in a neonate with hypergalactosaemia detected by mass screening.' J Inherit Metab Dis 25(1): 71-6. 18. Ohura, T., K. Kobayashi, et al. (2003). 'A novel inborn error of metabolism detected by elevated methionine and/or galactose in newborn screening: neonatal intrahepatic cholestasis caused by citrin deficiency.' Eur J Pediatr 162(5): 317-22. 19. Ohura, T., K. Kobayashi, et al. (2001). 'Neonatal presentation of adult-onset type II citrullinemia.' Hum Genet 108(2): 87-90. 20. Saheki, T., K. Inoue, et al. 'Citrin deficiency and current treatment concepts.' Mol Genet Metab 100 Suppl 1: S59-64. 21. Saheki, T. and K. Kobayashi (2002). 'Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD).' J Hum Genet 47(7): 333-41. 22. Saheki, T., K. Kobayashi, et al. (2004). 'Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle.' Mol Genet Metab 81 Suppl 1: S20-6. 23. Saheki, T., K. Kobayashi, et al. (2005). 'Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier.' Hepatol Res 33(2): 181-4. 24. Tabata, A., J. S. Sheng, et al. (2008). 'Identification of 13 novel mutations including a retrotransposal insertion in SLC25A13 gene and frequency of 30 mutations found in patients with citrin deficiency.' J Hum Genet 53(6): 534-45. 25. Tamamori, A., A. Fujimoto, et al. (2004). 'Effects of citrin deficiency in the perinatal period: feasibility of newborn mass screening for citrin deficiency.' Pediatr Res 56(4): 608-14. 26. Tamamori, A., Y. Okano, et al. (2002). 'Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation.' Eur J Pediatr 161(11): 609-13. 27. Tazawa, Y., D. Abukawa, et al. (2005). 'A possible mechanism of neonatal intrahepatic cholestasis caused by citrin deficiency.' Hepatol Res 31(3): 168-71. 28. Tokuhara, D., M. Iijima, et al. (2007). 'Novel diagnostic approach to citrin deficiency: analysis of citrin protein in lymphocytes.' Mol Genet Metab 90(1): 30-6. 29. Tsai, C. W., C. C. Yang, et al. (2006). 'Homozygous SLC25A13 mutation in a Taiwanese patient with adult-onset citrullinemia complicated with steatosis and hepatocellular carcinoma.' J Formos Med Assoc 105(10): 852-6. 30. Wen, P. Q., G. B. Wang, et al. 'SLC25A13 gene analysis in neonates with intrahepatic cholestasis caused by citrin deficiency' Zhongguo Dang Dai Er Ke Za Zhi 13(4): 303-8. 31. Yamaguchi, N., K. Kobayashi, et al. (2002). 'Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: Identification of two novel mutations and establishment of multiple DNA diagnosis methods for nine mutations.' Hum Mutat 19(2): 122-30. 32. Yasuda, T., N. Yamaguchi, et al. (2000). 'Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia.' Hum Genet 107(6): 537-45. 33. Yazaki, M., Y. Takei, et al. (2005). 'Risk of worsened encephalopathy after intravenous glycerol therapy in patients with adult-onset type II citrullinemia (CTLN2).' Intern Med 44(3): 188-95. 34. Yeh, J. N., Y. M. Jeng, et al. (2006). 'Hepatic steatosis and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in Taiwanese infants.' J Pediatr 148(5): 642-6. 35. Website of GeneReviews : citrin deficiency 36. 代謝性疾病 台灣經驗 行政院衛生署國民健康局出版 37. 認識罕見疾病(I) 財團法人罕見疾病基金會/台大醫院基因醫學部 印行 38. 網路維基百科:Positive predictive value http://en.wikipedia.org/wiki/Positive_predictive_value | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46898 | - |
dc.description.abstract | 背景
Citrin缺乏症是尿素代謝循環異常疾病之一,由於負責製造Citrin蛋白的SLC25A13基因突變而造成疾病產生。Citrin缺乏症主要有兩種症狀表現:第二型瓜胺酸血症及新生兒膽汁鬱積症。並非所有Citrin缺乏症個案在新生兒時期會出現瓜胺酸血症之症狀,因此導致Citrin缺乏症在新生兒篩檢的檢出率並不高。本實驗設計出一組SLC25A13基因突變熱點檢測搭配合原本的新生兒篩檢系統,希望能藉此提高台灣新生兒篩檢對於Citrin缺乏症之偵測率。 方法 本實驗針對3個在台灣最常出現的SLC25A13基因突變熱點設計一組基因突變檢測。實驗檢測對象為新生兒篩檢初檢結果出現瓜胺酸濃度異常之新生兒個案,取其初檢血片萃取DNA後,實行SLC25A13基因突變熱點檢測。突變檢測結果為陽性個案便通知回診接受確認診斷;其餘檢測結果為陰性個案其後續之檢驗流程則回歸原本新生兒篩檢報告系統。 結果 實驗期間從民國99年3月28日到99年12月31日為止,台大醫院新生兒篩檢中心共46,699名新生兒中,有313位符合受檢條件之新生兒個案接受進入本研究。突變檢測結果共找到2位Compound mutation heterozygote 個案,7位Mutant heterozygote個案。經確認診斷後,共計4位Citrin缺乏症陽性個案。而實驗期間,亦有4位突變檢測陰性個案經原本新生兒篩檢系統確診為Citrin缺乏症陽性個案,全部總計有8位Citrin缺乏症個案。本實驗設計之檢測方法對於Citrin缺乏症之陽性偵測率為75%。 結論 本實驗設計確實成功提高了新生兒篩檢對於Citrin缺乏症之偵測率(從25%提高至75%)。本實驗設計之主軸可做為未來實際應用之參考,假若再使用其他偵測度更高的突變分析方法,應可達到更好的疾病檢測效果。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-06-15T05:42:57Z (GMT). No. of bitstreams: 1 ntu-100-P98448007-1.pdf: 2455816 bytes, checksum: a12db83d92ba34c9cbd14fb80cf8bec0 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 口試委員會審定書 I
致謝 II 目錄 III 中文摘要 VII Abstract IX 第一章 緒論 1 第一節 Citrin缺乏症 1 第二節 新生兒篩檢 6 第三節 Citrin缺乏症之新生兒篩檢 8 第二章 研究動機與目的 9 第一節 研究動機 9 第二節 研究目的 9 第三節 實驗假說 10 第三章 實驗方法與材料 11 第一節 實驗對象與實驗設計 11 第二節 突變分析及實驗材料 13 第三節 實驗品質管制 24 第四章 實驗結果 26 第一節 乾燥濾紙血片萃取DNA 26 第二節 PCR反應條件測試 27 第三節 突變檢測實驗結果 29 第四節 Citrin缺乏症確認個案資料及檢驗數據 34 第五節 實驗假說檢定及統計分析 36 第五章 實驗結果討論 38 第一節 血片萃取DNA成功率 38 第二節 實驗對象篩檢條件之訂定 39 第三節 突變檢測效力之分析 42 第四節 突變基因頻率之討論 43 第五節 本方法於新生兒篩檢之實際應用 44 第六章 未來與展望 46 參考文獻 47 | |
dc.language.iso | zh-TW | |
dc.title | Citrin缺乏症在新生兒篩檢的基因突變研究 | zh_TW |
dc.title | Mutation study of citrin deficiency in newborn screening | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳慧玲(Huey-Ling Chen),簡穎秀(Yin-Hsiu Chien) | |
dc.subject.keyword | Citrin缺乏症,第二型瓜胺酸血症,新生兒膽汁鬱積症,新生兒篩檢,SLC25A13基因, | zh_TW |
dc.subject.keyword | Citrin deficiency,Citrullinemia type II (CTLN2),Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD),newborn screening,SLC25A13, | en |
dc.relation.page | 51 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-19 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
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