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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 | Nien-I Chen | en |
dc.contributor.author | 陳念宜 | zh_TW |
dc.date.accessioned | 2021-06-13T15:41:16Z | - |
dc.date.available | 2011-10-05 | |
dc.date.copyright | 2011-10-05 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-22 | |
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Longo, Tyrosine residues affecting sodium stimulation of carnitine transport in the OCTN2 carnitine/organic cation transporter. J Biol Chem, 2004. 279(8): p. 7247-53. 16. Wang, Y., et al., Phenotype and genotype variation in primary carnitine deficiency. Genet Med, 2001. 3(6): p. 387-92. 17. Dobrowolski, S.F., et al., Validation of dye-binding/high-resolution thermal denaturation for the identification of mutations in the SLC22A5 gene. Human Mutation, 2005. 25(3): p. 306-13. 18. Koizumi, A., et al., Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency. Hum Mol Genet, 1999. 8(12): p. 2247-54. 19. Wilcken, B., et al., Carnitine transporter defect diagnosed by newborn screening with electrospray tandem mass spectrometry. J Pediatr, 2001. 138(4): p. 581-4. 20. Schimmenti, L.A., et al., Expanded newborn screening identifies maternal primary carnitine deficiency. 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Seth, P., et al., Mutations in novel organic cation transporter (OCTN2), an organic cation/carnitine transporter, with differential effects on the organic cation transport function and the carnitine transport function. J Biol Chem, 1999. 274(47): p. 33388-92. 26. Nezu, J., et al., Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet, 1999. 21(1): p. 91-4. 27. Mayatepek, E., et al., Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency. Human Mutation, 2000. 15(1): p. 118. 28. Makhseed, N., et al., Carnitine transporter defect due to a novel mutation in the SLC22A5 gene presenting with peripheral neuropathy. Journal of Inherited Metabolic Disease, 2004. 27(6): p. 778-80. 29. Lamhonwah, A.M., et al., Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy. Am J Med Genet, 2002. 111(3): p. 271-84. 30. Longo, N., et al., Disorders of carnitine transport and the carnitine cycle. American Journal of Medical Genetics Part C, Seminars in Medical Genetics, 2006. 142C(2): p. 77-85. 31. Wang, Y., T.A. Meadows, and N. Longo, Abnormal sodium stimulation of carnitine transport in primary carnitine deficiency. J Biol Chem, 2000. 275(27): p. 20782-6. 32. Shekhawat, P.S., et al., Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2(-/-)) mice. Molecular Genetics & Metabolism, 2007. 92(4): p. 315-24. 33. Tang, N.L., et al., A founder mutation (R254X) of SLC22A5 (OCTN2) in Chinese primary carnitine deficiency patients. Human Mutation, 2002. 20(3): p. 232. 34. Lamhonwah, A.M., et al., OCTN2 mutation (R254X) found in Saudi Arabian kindred: recurrent mutation or ancient founder mutation? Journal of Inherited Metabolic Disease, 2004. 27(4): p. 473-6. 35. Novak, M., et al., Carnitine in the perinatal metabolism of lipids. I. Relationship between maternal and fetal plasma levels of carnitine and acylcarnitines. Pediatrics, 1981. 67(1): p. 95-100. 36. Cederblad, G., et al., Carnitine in maternal and neonatal plasma. Acta Paediatr Scand, 1985. 74(4): p. 500-4. 37. El-Hattab, A.W., et al., Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects. Genet Med. 12(1): p. 19-24. 38. 胡務亮, et al., Carnitine Transport Defect Presenting with Hyperammonemia: Report of One Case. Acta Paediatrica Taiwanica, 2000. 41(1): p. 36-38. 39. 王舒眉, 侯家瑋, and 林如立, A Retrospective Epidemiological and Etiological Study of Metabolic Disorders in Children with Cardiomyopathies. Acta Paediatrica Taiwanica, 2006. 47(2): p. 83-87. 40. Lee, N.C., et al., Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening. Molecular Genetics & Metabolism. 100(1): p. 46-50. 41. Shenai, J.P., et al., Carnitine Status at Birth of Newborn Infants of Varying Gestation. Pediatric Research, 1983. 17(7): p. 579-582. 42. Crill, C.M., et al., Relative bioavailability of carnitine supplementation in premature neonates. JPEN J Parenter Enteral Nutr, 2006. 30(5): p. 421-5. 43. Bishop Hubbard, H., Policy issues related to expanded newborn screening: a review of three genetic/metabolic disorders. Policy Polit Nurs Pract, 2007. 8(3): p. 201-9. 44. Schulpis, K.H., et al., The effect of the mode of delivery on the maternal-neonatal carnitine blood levels and antioxidant status, in Clinical Chemistry & Laboratory Medicine. 2008, De Gruyter. p. 680-686. 45. Li, F.Y., et al., Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency. Human Mutation. 31(8): p. E1632-51. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37739 | - |
dc.description.abstract | 背景:
原發性肉鹼缺乏症是因為細胞膜上的肉鹼運輸器有缺陷,導致肉鹼由尿液排出,造成體內肉鹼缺乏所引起的一種體染色體隱性遺傳的脂肪酸代謝異常疾病。目前藉由新生兒篩檢系統,使用串聯質譜儀來偵測血片游離肉鹼濃度,可發現尚未出現徵狀的新生兒與母親。但也因為母血效應的影響,暗示有部分的患嬰無法被篩檢出來,有偽陰性存在。 方法: 本研究是在篩檢流程上利用串聯質譜儀分析血片的游離肉鹼濃度進行初篩,首先調高cut-offs,再搭配在臺灣新生兒常見的突變基因p.R254X分析,做為第二線的篩檢工具,希望能提高新生兒篩檢在原發性肉鹼缺乏症的検出率。 結果: 我們在30,237個新生兒當中有206件因為游離肉鹼濃度初檢數值低於cut-offs,需要複檢而進入p.R254X基因分析。實驗結果顯示,發現12個帶有p.R254X突變基因的帶原者,得到p.R254X基因帶原率是1/2,520。然而,另外發現1個確認陽性個案,但其突變基因型卻不包含p.R254X。預估原發性肉鹼缺乏症在臺灣的發生率是1/30,237。 結論與展望: 對於原發性肉鹼缺乏症的篩檢,使用串聯質譜儀偵測血液的游離肉鹼濃度仍是一個可靠的方法。雖然本研究未能增加此症之檢出率,但原發性肉鹼缺乏症是一個很重要的疾病,未來仍需繼續努力。 | zh_TW |
dc.description.abstract | Background:Primary carnitine deficiency (PCD) is an autosomal recessive fatty acid oxidation disease caused by a defect of carnitine transporter across the cell membrane, and then carnitine is excreted through the kidney and intracellular carnitine is deficiency. Tandem mass spectrometry (MS/MS) screening of newborns can detect both asymptomatic newborns and mothers, but the maternal effects may be one of the reasons for false-negative.
Methods:We first used MS/MS to measure free carnitine level in dried blood spots. We elevated the free carnitine cut-offs, and then combined p.R254X molecular analysis as the second tier analysis tool in the newborn screening flow-chart. Because of p.R254X is the most common mutation in Taiwanese newborns. The goal is to improve the detection rates of PCD. Results:Out of 30,237 newborn, there were 206 samples which free carnitine levels lower than the cut-offs in the initial screening card and the follow-up samples were requested. We found 12 heterozygote of p.R254X, the carrier rate of p.R254X was 1/2,520.Among them, however, only one newborn was confirmed as a case of PCD, whose genotype dose not contain p.R254X. Therefore, the incidence of newborn with PCD in this study is 1/30,237. Conclusion:The MS/MS is still a reliable method for detecting PCD.PCD is a very serious disease. Although this study failed to enhance the detection rate of this disease, we should continue to make more discoveries and put more efforts in this study. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:41:16Z (GMT). No. of bitstreams: 1 ntu-100-P98448006-1.pdf: 1586449 bytes, checksum: 7e5dff25a1d8acc92af93171777bcb2b (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 口試委員審定書 II
誌 謝 III 中文摘要 VIII ABSTRACT IX 論文正文 1 第壹章、 緒論 1 壹.1. 新生兒篩檢 1 壹.2. 肉鹼與脂肪酸氧化 4 壹.3. 原發性肉鹼缺乏症 6 壹.4. OCTN2基因 9 壹.5. 原發性肉鹼缺乏症的母親造成寶寶偽陽性與母血效應干擾造成寶寶偽陰性的發現 11 第貳章、 研究動機及目的 13 貳.1. 研究動機 13 貳.2. 研究目的 13 第參章、 研究方法 14 參.1. 實驗設計 14 參.2. 實驗材料 15 參.3. 實驗方法 17 第肆章、 結果 23 肆.1. 血片DNA萃取方式測試 23 肆.2. 血片使用原液與稀釋液進行PCR的效率不同 23 肆.3. 血片分析P.R254X突變基因之帶因者頻率 23 肆.4. 帶因者的游離肉鹼數值及P.R254X突變之關聯性 24 肆.5. 串聯質譜儀之游離肉鹼數值分析 24 第伍章、 討論 27 伍.1. 血片萃取DNA 27 伍.2. PCR-RFLP方法之優缺點 27 伍.3. 早產兒之游離肉鹼數值 27 伍.4. P.R254X突變基因之頻率與文獻報告的比較 28 伍.5. P.R254X分子檢測原發性肉鹼缺乏症之篩檢檢出率 28 伍.6. 原發性肉鹼缺乏症的發生率 29 伍.7. 原發性肉鹼缺乏症的基因型 30 第陸章、 結論與展望 31 第柒章、 參考文獻 32 第捌章、 圖表 35 | |
dc.language.iso | zh-TW | |
dc.title | 新生兒篩檢原發性肉鹼缺乏症R254X基因突變之研究 | zh_TW |
dc.title | R254X Mutation Study of Primary Carnitine Deficiency
in Newborn screening | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 簡穎秀(Yin-Hsiu Chien),林銘泰(Ming-Tai Lin) | |
dc.subject.keyword | 新生兒篩檢,原發性肉鹼缺乏症,游離肉鹼,母血效應,OCTN2基因,p.R254X突變, | zh_TW |
dc.subject.keyword | newborn screening,primary carnitine deficiency,free carnitine,maternal effect,OCTN2 gene,p.R254X mutation, | en |
dc.relation.page | 48 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-22 | |
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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