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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 簡穎秀(Yin-Hsiu Chien) | |
| dc.contributor.author | Min-Huei Hu | en |
| dc.contributor.author | 胡閔慧 | zh_TW |
| dc.date.accessioned | 2021-06-15T06:14:20Z | - |
| dc.date.available | 2010-09-09 | |
| dc.date.copyright | 2010-09-09 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-08-11 | |
| dc.identifier.citation | Andria A, Fowler B, Sebastio G. Disorders of sulfur amino acid metabolism. In: Fernandes J,Saudubray JM, Van den Berghe G, eds. Inborn Metabolic Diseases., 3rd ed. Hong-Kong: Springer. 2000:233-240.
Calonge N, Green NS, Rinaldo P, Lloyd-Puryear M, Dougherty D, Boyle C, Watson M, Trotter T, Terry SF, Howell RR. 2010. Committee report: Method for evaluating conditions nominated for population-based screening of newborns and children. Genet Med. Cheng KH, Hung MC, Chen SJ, Kao CH, Niu DM. 2007. Lenticular subluxation in a patient with homocystinuria undetected by neonatal screening. J Chin Med Assoc 70(12):562-4. Chien YH, Chiang SC, Huang A, Hwu WL. 2005. Spectrum of hypermethioninemia in neonatal screening. Early Hum Dev 81(6):529-33. Chien YH, Chiang SC, Zhang XK, Keutzer J, Lee NC, Huang AC, Chen CA, Wu MH, Huang PH, Tsai FJ and others. 2008. Early detection of Pompe disease by newborn screening is feasible: results from the Taiwan screening program. Pediatrics 122(1):e39-45. Chu SY, Tsai WY, Chen LH, Wei ML, Chien YH, Hwu WL. 2002. Neonatal screening for congenital adrenal hyperplasia in Taiwan: a pilot study. J Formos Med Assoc 101(10):691-4. El-Said MF, Badii R, Bessisso MS, Shahbek N, El-Ali MG, El-Marikhie M, El-Zyoid M, Salem MS, Bener A, Hoffmann GF and others. 2006. A common mutation in the CBS gene explains a high incidence of homocystinuria in the Qatari population. Hum Mutat 27(7):719. Gan-Schreier H, Kebbewar M, Fang-Hoffmann J, Wilrich J, Abdoh G, Ben-Omran T, Shahbek N, Bener A, Al Rifai H, Al Khal AL and others. 2010. Newborn population screening for classic homocystinuria by determination of total homocysteine from Guthrie cards. J Pediatr 156(3):427-32. Gaustadnes M, Ingerslev J, Rutiger N. 1999. Prevalence of congenital homocystinuria in Denmark. N Engl J Med 340(19):1513. Huang HP, Chu KL, Chien YH, Wei ML, Wu ST, Wang SF, Hwu WL. 2006. Tandem mass neonatal screening in Taiwan--report from one center. J Formos Med Assoc 105(11):882-6. Hwu W. Neonatal screening in Taiwan; 2004; Shanghai, China. Hou JW, Wang TR, Pyridoxine-responsive homocystinuria with ruptured sinus of Valsalva in a Chinese boy. J Inherit Metab Dis 1994; 17(6): 759. Kery V, Bukovska G, Kraus JP. 1994. Transsulfuration depends on heme in addition to pyridoxal 5'-phosphate. Cystathionine beta-synthase is a heme protein. J Biol Chem 269(41):25283-8. Kraus JP, Oliveriusova J, Sokolova J, Kraus E, Vlcek C, de Franchis R, Maclean KN, Bao L, Bukovsk, Patterson D and others. 1998. The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms. Genomics 52(3):312-24. Lee SJ, Lee DH, Yoo HW, Koo SK, Park ES, Park JW, Lim HG, Jung SC. 2005. Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria. J Hum Genet 50(12):648-54. Lu YH YH, Lo MY, Gao JH, Hsu JH, Chong KW, Kao CH, Cheng KH, Liu TT, Hung PY, Niu DM. 2008. The high incidence of homocystinuria in the Tao tribe of Taiwan. ICIEM. p 13. Lu CY, Hou JW, Wang PJ, Chiu HH, Wang TR. Homocystinuria presenting as fatal common carotid artery occlusion. Pediatr Neurol 1996; 15(2):159-62. Mudd SL, HL; Kraus, JP. 2001. Disorders of Transsulfuration. In: Scriver CR BA, Sly WS, Valle D, eds., editor. The metabolic and molecular basis of inherited disease. New York: McGraw Hill. p 2007-2056. Munke M, Kraus JP, Ohura T, Francke U. 1988. The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17. Am J Hum Genet 42(4):550-9. Mudd SH. Levy HL. Tengerman A. Boujet C. Buist N. Davidson-Mundt A. Hudgins L. Oyanagi K. Nagao M. Wilsoon WG. Isolated persistent hypermethioninemia. American Journal of Human Genetics. 1995; 57 (4): 882-892. Naughten ER, Yap S, Mayne PD. 1998. Newborn screening for homocystinuria: Irish and world experience. Eur J Pediatr 157 Suppl 2:S84-7. Peterschmitt MJ, Simmons JR, Levy HL. 1999. Reduction of false negative results in screening of newborns for homocystinuria. N Engl J Med 341(21):1572-6. Refsum H, Fredriksen A, Meyer K, Ueland PM, Kase BF. 2004. Birth prevalence of homocystinuria. J Pediatr 144(6):830-2. Surtees R. Leonard J. Austin S. Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway. Lancet. 1991; 338: 1550-1554. Watanabe T, Kuroda Y, Naito E, Ito M, Takeda E, Toshima K, Miyao M, Tomita T, Furukawa S. 1987. Urinary homocystine levels in a newborn infant with cystathionine synthase deficiency. Eur J Pediatr 146(4):436-8. Yap S. Naughten E. Homocystinuria due to cystathionine beta-synthase deficiency in Ireland: 25 years' experience of a newborn screened and treated population with reference to clinical outcome and biochemical control. Journal of Inherited Metabolic Disease. 1998; 21 (7) : 738-747. 牛道明, 鄭麗妹, 江傳箕. 2009. 高胱胺酸尿症病患照護之介入研究-以蘭嶼鄉為例. 台北榮民總醫院小兒部. 行政院衛生署國民健康局（2004）代謝性疾病 台灣經驗 行政院衛生署. 新生兒先天性代謝異常疾病篩檢作業手冊. 2009,2. 蔣思慧、蕭廣仁. 國內新生兒先天代謝異常疾病篩檢項目增減可行性之探討。2005; 台北. p 53-76. 行政院原住民委員會 http://www.apc.gov.tw/main/index.jsp 台東縣政府.原住民族全球資訊網. http://www.taitung.gov.tw/Aborigine/index.aspx. 蘭嶼全球資訊網 http://lanyu.taitung.gov.tw/ | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47715 | - |
| dc.description.abstract | 背景:因為典型高胱胺酸尿症在台灣地區住民特定族群中有好發的突變點，而且其盛行率與經由新生兒篩檢的發生率相距甚大，因此現行新生兒篩檢方式的敏感性需要被重新檢視。
方法:本研究以基因分析搭配甲硫胺酸數值分析，檢驗台灣地區新生兒 1.p.D47E突變的帶因率; 2.台灣地區新生兒篩檢採用甲硫胺酸做為標誌物是否無法偵測p.D47E突變的典型高胱胺酸患者。 結果:新生兒篩檢血片抽取的DNA可以用allelic specific PCR的方式，找到適當的條件後，進行大量檢體的篩檢已知單點鹼基突變。實驗結果顯示，檢測3357個來自抽樣地區(台東)的新生兒，只有2人為帶有此突變的帶因者，帶因率為1/3357，預估的疾病發生率約低於百萬分之一。 結論與展望:本實驗的結果顯示，CBS基因p. D47E突變在台東地區的帶因率僅1/3,357；因此預測此種患者在全台地區的盛行率極低，目前新生兒篩檢仍不須加做基因突變分析或改用血片高胱胺酸濃度篩檢以減少偽陰性率。未來對於高胱胺酸尿症患者的篩檢策略是否需要調整，例如全面改以血片高胱胺酸濃度篩檢，基因篩檢或是針對特定族群使用不同的篩檢策略，將需要進一步研究分析，以提供公共衛生政策參考。 | zh_TW |
| dc.description.abstract | Background: A mutation of the CBS gene associated with classical homocystinuria been discovered in Taiwan. The high incidence of the gene however, is inconsistent with results of neonatal screening, indicating that the sensitivity of the current protocol (methionine levels detected by tandem mass spectrometry) should be reassessed. In this research, we proposed that tandem mass spectrometry coupled with the allelic-specific PCR could make an early recognition easier and more reliable.
Methods: In this study, we determined the carrier rate of p.D47E mutation by allelic-specific PCR, by establishing relationship between the p.D47E mutation and levels of methionine detected through tandem mass spectrometry. Results: Genomic DNA from blood spots was proven suitable for allelic-specific PCR. Wide scale screening for p.D47E mutation was performed, and results showed that only 2 out of 3,357 newborns from the Taitung area were heterozygous carries. The carrier rate of p.D47E mutation was 1/3,357, making the estimated incidence of homocystinuria less than one in a million. The levels of homocysteine in these two heterozygous carriers has not increased. Conclusion: Our data indicated that the carrier rate of the p.D47E mutation of CBS gene in the Taitung area was only 1 out of 3,357, which indicated a low prevalence in Taiwan. As a result, it is our opinion that including point-mutation genetic assay for homocysteine is unnecessary for the screening newborns in Taiwan. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T06:14:20Z (GMT). No. of bitstreams: 1 ntu-99-P97448006-1.pdf: 2602157 bytes, checksum: 28cb82e4e682d423a29f43dd3053bcd6 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 4 英文摘要 5 論文本文 壹.1. 新生兒先天代謝異常疾病篩檢 6 壹.2. 典型高胱胺酸尿症 8 壹.3. 高胱胺酸尿症的篩檢方法 12 壹.4. 台灣地區高胱胺酸尿症篩檢的現狀 13 第貳章、 研究動機及目的 14 貳.1. 研究動機 14 貳.2. 研究目的 14 第參章、 實驗材料與研究方法 15 參.1. 實驗設計 15 參.2. 實驗材料 16 參.3. 實驗方法 25 第肆章、 結果 37 肆.1. 血片DNA萃取測試 37 肆.2. 血片DNA稀釋濃度測試 40 肆.3. Allelic-specific PCR 條件測試 41 肆.4. Allelic-specific PCR結果與基因定序結果比較 43 肆.5. 血片分析p.D47E突變基因之頻率 44 肆.6. 帶因者的甲硫胺酸數值分析 44 肆.7. 甲硫胺酸（MET）數值分析 45 第伍章、 討論 51 伍.1. 血片萃取DNA 51 伍.2. Allelic specific PCR 方法的優缺點 52 伍.3. Allelic Specific PCR 與Real-Time PCR的比較 52 伍.4. 取樣方法的優缺點 53 伍.5. 發生率與實際狀況不相符 53 伍.6. 甲硫胺酸篩檢高胱胺酸尿症的患者的效力 54 第陸章、 結論與展望 57 參考文獻、 58 | |
| dc.language.iso | zh-TW | |
| dc.subject | 高胱胺酸尿症 | zh_TW |
| dc.subject | 台東地區 | zh_TW |
| dc.subject | 新生兒篩檢 | zh_TW |
| dc.subject | 甲硫胺酸 | zh_TW |
| dc.subject | Taitung | en |
| dc.subject | Newborn screening | en |
| dc.subject | Homocystinuria | en |
| dc.subject | Methionine | en |
| dc.title | 新生兒篩檢個案CBS基因缺陷研究-以戶籍台東個案為主 | zh_TW |
| dc.title | Newborn Screening Case Study of CBS Gene Defect-
Case Based on Household Registration in Taitung | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 胡務亮(Wuh-Liang Hwu),張雅雯(Ya-Wen Chang) | |
| dc.subject.keyword | 新生兒篩檢,高胱胺酸尿症,甲硫胺酸,台東地區, | zh_TW |
| dc.subject.keyword | Newborn screening,Homocystinuria,Methionine,Taitung, | en |
| dc.relation.page | 60 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-08-12 | |
| 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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