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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李建南 | zh_TW |
dc.contributor.advisor | Chien-Nan Lee | en |
dc.contributor.author | 王郁筑 | zh_TW |
dc.contributor.author | Yu-Chu Wang | en |
dc.date.accessioned | 2021-07-11T15:37:01Z | - |
dc.date.available | 2024-02-28 | - |
dc.date.copyright | 2018-10-09 | - |
dc.date.issued | 2018 | - |
dc.date.submitted | 2002-01-01 | - |
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Murray, Nonlinear association between CGG repeat number and age of menopause in FMR1 premutation carriers. Eur J Hum Genet, 2006. 14(2): p. 253-5. 15. Sullivan, A.K., et al., Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod, 2005. 20(2): p. 402-12. 16. Thurman, A.J., et al., Noncomprehension Signaling in Males and Females With Fragile X Syndrome. J Speech Lang Hear Res, 2017. 60(6): p. 1606-1621. 17. Rousseau, F., et al., Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. N Engl J Med, 1991. 325(24): p. 1673-81. 18. Gold, B., et al., Diagnosis of Fragile X syndrome by Southern blot hybridization using a chemiluminescent probe: a laboratory protocol. Mol Diagn, 2000. 5(3): p. 169-78. 19. Hayward, B.E., D. Kumari, and K. Usdin, Recent advances in assays for the fragile X-related disorders. Hum Genet, 2017. 136(10): p. 1313-1327. 20. Fry, M. and L.A. Loeb, The fragile X syndrome d(CGG)n nucleotide repeats form a stable tetrahelical structure. Proc Natl Acad Sci U S A, 1994. 91(11): p. 4950-4. 21. Usdin, K. and K.J. Woodford, CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro. Nucleic Acids Res, 1995. 23(20): p. 4202-9. 22. Brown, W.T., et al., Prenatal diagnosis and carrier screening for fragile X by PCR. Am J Med Genet, 1996. 64(1): p. 191-5. 23. Saluto, A., et al., An enhanced polymerase chain reaction assay to detect pre- and full mutation alleles of the fragile X mental retardation 1 gene. J Mol Diagn, 2005. 7(5): p. 605-12. 24. Tassone, F., et al., A rapid polymerase chain reaction-based screening method for identification of all expanded alleles of the fragile X (FMR1) gene in newborn and high-risk populations. J Mol Diagn, 2008. 10(1): p. 43-9. 25. Cheng, Y.K., et al., Identification of fragile X pre-mutation carriers in the Chinese obstetric population using a robust FMR1 polymerase chain reaction assay: implications for screening and prenatal diagnosis. Hong Kong Med J, 2017. 23(2): p. 110-6. 26. Nygren, A.O., S.I. Lens, and R. Carvalho, Methylation-specific multiplex ligation-dependent probe amplification enables a rapid and reliable distinction between male FMR1 premutation and full-mutation alleles. J Mol Diagn, 2008. 10(6): p. 496-501. 27. Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol, 2017. 129(3): p. e41-e55. 28. Sherman, S., B.A. Pletcher, and D.A. Driscoll, Fragile X syndrome: Diagnostic and carrier testing. Genetics in Medicine, 2005. 7(8): p. 584-587. 29. Bailey, D.B., Jr., et al., No change in the age of diagnosis for fragile x syndrome: findings from a national parent survey. Pediatrics, 2009. 124(2): p. 527-33. 30. Bailey, D.B., Jr., D. Skinner, and K.L. Sparkman, Discovering fragile X syndrome: family experiences and perceptions. Pediatrics, 2003. 111(2): p. 407-16. 31. Abrams, L., et al., Newborn, carrier, and early childhood screening recommendations for fragile X. Pediatrics, 2012. 130(6): p. 1126-35. 32. Hill, M.K., et al., A systematic review of population screening for fragile X syndrome. Genet Med, 2010. 12(7): p. 396-410. 33. Finucane, B., et al., Genetic counseling and testing for FMR1 gene mutations: practice guidelines of the national society of genetic counselors. J Genet Couns, 2012. 21(6): p. 752-60. 34. Willemsen, R., et al., Timing of the absence of FMR1 expression in full mutation chorionic villi. Hum Genet, 2002. 110(6): p. 601-5. 35. Alfirevic, Z., K. Sundberg, and S. Brigham, Amniocentesis and chorionic villus sampling for prenatal diagnosis. Cochrane Database Syst Rev, 2003(3): p. CD003252. 36. Stern, H.J., Preimplantation Genetic Diagnosis: Prenatal Testing for Embryos Finally Achieving Its Potential. J Clin Med, 2014. 3(1): p. 280-309. 37. Miclea, D., et al., Genetic testing in patients with global developmental delay / intellectual disabilities. A review. Clujul Med, 2015. 88(3): p. 288-92. 38. Chonchaiya, W., A. Schneider, and R.J. Hagerman, Fragile X: a family of disorders. Adv Pediatr, 2009. 56: p. 165-86. 39. Fernandez, B.A. and S.W. Scherer, Syndromic autism spectrum disorders: moving from a clinically defined to a molecularly defined approach. Dialogues Clin Neurosci, 2017. 19(4): p. 353-371. 40. Raspa, M., A.C. Wheeler, and C. Riley, Public Health Literature Review of Fragile X Syndrome. Pediatrics, 2017. 139(Suppl 3): p. S153-S171. 41. Hammond, L.S., et al., Fragile X syndrome and deletions in FMR1: new case and review of the literature. Am J Med Genet, 1997. 72(4): p. 430-4. 42. de Graaff, E., et al., Hotspot for deletions in the CGG repeat region of FMR1 in fragile X patients. Hum Mol Genet, 1995. 4(1): p. 45-9. 43. Toledano-Alhadef, H., et al., Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. Am J Hum Genet, 2001. 69(2): p. 351-60. 44. Berkenstadt, M., et al., Preconceptional and prenatal screening for fragile X syndrome: experience with 40,000 tests. Prenat Diagn, 2007. 27(11): p. 991-4. 45. Ryynanen, M., et al., Feasibility and acceptance of screening for fragile X mutations in low-risk pregnancies. Eur J Hum Genet, 1999. 7(2): p. 212-6. 46. Rousseau, F., et al., Prevalence of carriers of premutation-size alleles of the FMRI gene--and implications for the population genetics of the fragile X syndrome. Am J Hum Genet, 1995. 57(5): p. 1006-18. 47. Levesque, S., et al., Screening and instability of FMR1 alleles in a prospective sample of 24,449 mother-newborn pairs from the general population. Clin Genet, 2009. 76(6): p. 511-23. 48. Hantash, F.M., et al., FMR1 premutation carrier frequency in patients undergoing routine population-based carrier screening: insights into the prevalence of fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency in the United States. Genet Med, 2011. 13(1): p. 39-45. 49. Seltzer, M.M., et al., Prevalence of CGG expansions of the FMR1 gene in a US population-based sample. Am J Med Genet B Neuropsychiatr Genet, 2012. 159B(5): p. 589-97. 50. Tzeng, C.C., et al., A 15-year-long Southern blotting analysis of FMR1 to detect female carriers and for prenatal diagnosis of fragile X syndrome in Taiwan. Clin Genet, 2017. 92(2): p. 217-220. 51. Peprah, E., Fragile X syndrome: the FMR1 CGG repeat distribution among world populations. Ann Hum Genet, 2012. 76(2): p. 178-91. 52. Otsuka, S., et al., Fragile X carrier screening and FMR1 allele distribution in the Japanese population. Brain Dev, 2010. 32(2): p. 110-4. 53. Nolin, S.L., et al., Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles. Am J Hum Genet, 2003. 72(2): p. 454-64. 54. Gatta, V., et al., MS-MLPA analysis for FMR1 gene: evaluation in a routine diagnostic setting. BMC Med Genet, 2013. 14: p. 79. 55. Ouyang, L., et al., A comparison of family financial and employment impacts of fragile X syndrome, autism spectrum disorders, and intellectual disability. Res Dev Disabil, 2014. 35(7): p. 1518-27. 56. Metcalfe, S.A., et al., Informed decision making and psychosocial outcomes in pregnant and nonpregnant women offered population fragile X carrier screening. Genet Med, 2017. 19(12): p. 1346-1355. 57. Nazareth, T., et al., Burden of illness among patients with fragile X syndrome (FXS): a Medicaid perspective. Curr Med Res Opin, 2016. 32(3): p. 405-16. 58. Sacco, P., et al., The economic burden of fragile x syndrome: healthcare resource utilization in the United States. Am Health Drug Benefits, 2013. 6(2): p. 73-83. 59. Musci, T.J. and A.B. Caughey, Cost-effectiveness analysis of prenatal population-based fragile X carrier screening. Am J Obstet Gynecol, 2005. 192(6): p. 1905-12; discussion 1912-5. | - |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79018 | - |
dc.description.abstract | X染色體脆折症(Fragile X Syndrome, FXS)為最常見的遺傳性智能障礙疾病,約250位女性中有1位為X染色體脆折症帶因者,而母親CGG重複次數越多,將異常擴增遺傳給下一代患病機率則越高。
為統計漢人族群準突變及全突變帶因者發生率分析產前篩檢可行性、成本效益、優勢,本研究資料蒐集自2014年09月至2017年10月份共23,468位成年女性及其帶因者下一代之X染色體脆折症結果。以周邊血液進行DNA萃取後以商業化的試劑組進行聚合酶鏈鎖反應檢測FMR1基因CGG重複次數。 結果顯示最常見的等位基因(Allele)為29次重複(39.75%),其次為30次(25.36%)及28次(8.59%)。32位準突變帶因者,其中19次懷孕(52.8%)將異常擴增等位基因遺傳給下一代,而擴增為全突變則有6次。而有9位母親CGG重複次數大於69並將異常擴增等位基因遺傳給下一代,且擴增為全突變有6次。一名無症狀的全突變女性具有280次CGG重複的等位基因,第一胎產前檢測胎兒結果為5’UTR和第一外顯子具缺失的男性而中止妊娠,第二胎則為全突變女性胎兒。另一名無症狀的5’UTR和未知CGG重複序列上游缺失女性,其男性胎兒遺傳了此缺失等位基因而中止妊娠。 各族群FXS流行率皆不同,在此建立了漢人族群最大的帶因者篩檢研究,無症狀的準突變及全突變女性的聯合帶因率為0.14%(1/711),也為台灣的產前遺傳諮詢提供了相當重要的數據。 | zh_TW |
dc.description.abstract | Fragile X syndrome (FXS) is the most common cause of inherited intellectual and developmental disability. Approximately 1 in 250 females are carriers. The risk of transmitted from mother to offspring appear to be related to the size of the CGG repeat, with the highest risk associated with larger repeats.
Survey the prevalence of FXS Premutation (PM) and Full mutation (FM) carriers and the cost-effectiveness of the prenatal screening of FXS in a large Han Chinese cohort. This was a retrospective observational study including 23,468 Chinese women and offspring of carrier mothers between September 2014 and October 2017. The FMR1 CGG repeat status was determined using commercialized CGG repeat primed PCR with DNA extracted from peripheral blood. In our cohort, the most prevalent allele was 29 repeats (39.75%), followed by 30 (25.36%) and a minor allele was 28 repeats (8.59%). We identified 32 women with PM. The PM allele was transmitted to the fetus in 19 pregnancies (52.8%), and six of these 19 expanded to FM. Six of the nine maternal alleles that exceeded 69 repeats expanded to FM. One asymptomatic woman was found to have a FM allele with 280 CGG repeats. Her first pregnancy was terminated because prenatal genetic diagnosis revealed a male fetus carrying a FMR1 gene deletion of 5' UTR and exon 1. Her second fetus was a female carrying a FM allele as well. One asymptomatic women had a deletion of partial 5‘ UTR and upstream of unknown CGG repeats of FMR1 gene. The male fetus had inherited the deleted allele and was terminated. Population-based prevalence of FXS varied in countries. This is the largest study of the FXS carrier screening in Chinese women. The combined prevalence of PM and FM of FXS in normal asymptomatic Taiwanese women was as high as 0.14% (1 in 711) in this study. The reported FXS carrier rate in Taiwan is important for prenatal counseling. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T15:37:01Z (GMT). No. of bitstreams: 1 ntu-107-P05448007-1.pdf: 2850821 bytes, checksum: 1baebe2fa1e02475a90a8f298ea57b76 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 中文摘要 vi
Abstract vii 目錄 viii 第一章、 緒論 1 1.1 前言 1 1.2 X染色體脆折症簡介 1 1.2.1 FMR1基因、功能、調控機制 1 1.2.2 流行病學 2 1.2.3 基因分型 2 1.2.3.1 Normal 2 1.2.3.2 Intermediate 3 1.2.3.3 Premutation 3 1.2.3.4 FXTAS 4 1.2.3.5 FXPOI 5 1.2.3.6 Full mutation 5 1.2.4 Southern blotting 6 1.2.5 PCR 7 1.2.6 MS-MLPA 7 1.2.7 遺傳諮詢 7 1.2.7.1 產前檢查 8 1.2.7.2 胚胎著床前基因檢測 8 1.3 研究動機 9 1.3.1 發展遲緩、智能障礙與疾病關係 9 1.3.2 治療 9 第二章、 研究方法與材料 10 2.1 研究對象 10 2.2 研究方法 10 2.2.1 檢體類別 10 2.2.1.1 血液 10 2.2.1.2 羊膜穿刺 (羊水) 10 2.2.1.3 臍帶血 10 2.2.1.4 口腔黏膜細胞 10 2.2.1.5 血片 10 2.2.2 DNA 萃取 11 2.2.2.1 TANBead 11 2.2.2.2 Qiagen 13 2.2.3 FragilEase PCR 14 2.2.4 毛細管電泳 14 2.2.5 分析結果 15 第三章、 結果 16 3.1 X染色體脆折症成年女性FMR1基因分型 16 3.2 X染色體脆折症成年女性年齡分布 16 3.3 X染色體脆折症成年女性每年收案件數分布 16 3.4 X染色體脆折症成年女性台灣各區收案分布 17 3.5 X染色體脆折症成年女性Allele Frequency 17 3.6 X染色體脆折症成年女性及下一代基因分型結果 17 3.7 X染色體脆折症成年女性及下一代Transmitted of FMR1 alleles 18 3.8 分析X染色體脆折症成年女性及下一代遺傳風險 18 3.9 Full mutation maternal and offspring 19 3.9.1 Full mutation maternal and offspring綜合實驗結果 19 3.10 Partial deletion maternal and offspring 20 3.10.1 Partial deletion maternal and offspring綜合實驗結果 20 第四章、 討論與未來展望 21 4.1 各族群帶因者比例比較 21 4.2 Comparison of FMR1 allele frequencies 22 4.3 Comparison transmission of FMR1 allele to offspring 22 4.4 缺失型討論 23 4.5 實驗方法比較 23 4.5.1 南方墨點法 23 4.5.2 聚合酶鏈鎖反應 24 4.5.3 毛細管電泳 24 4.5.4 MS-MLPA 25 4.6 社會經濟效益 25 4.7 未來展望 26 4.7.1 整體社會成本 26 4.7.2 遺傳諮詢重要性 27 參考文獻 28 附錄 32 圖目錄 圖一. Southern blot實驗示意圖 32 圖二. X染色體脆折症篩檢流程示意圖 33 圖三. 毛細管電泳結果圖及標準曲線 34 圖四. Allele Frequency 35 圖五. 準突變母親結果追蹤樹狀圖 36 圖六. 全突變母親結果追蹤樹狀圖 37 圖七. 部分缺失型(其他)母親結果追蹤樹狀圖 38 圖八. Full mutation maternal and offspring pedigree 39 圖九. Full mutation maternal and offspring毛細管電泳結果圖 40 圖十. Deletion offspring MLPA結果圖 41 圖十一. Partial deletion maternal and offspring pedigree 41 圖十二. Partial deletion maternal and offspring 毛細管電泳結果圖 42 圖十三. Partial deletion maternal and offspring Southern blot 42 圖十四. Partial deletion maternal and offspring sanger sequence 43 圖十五. Partial deletion maternal and offspring sanger sequence 44 表目錄 表一. FMR1基因分型 45 表二. 女性遺傳下一代異常擴增風險 45 表三.成年女性基因分型 45 表四.成年女性與異常女性年齡分布結果 46 表五. X染色體脆折症成年女性每年收案件數分布 48 表六. X染色體脆折症成年女性台灣各區收案分布 49 表七.成年女性基因分型及下一代分型及結果 50 表八. Transmitted of FMR1 alleles 51 表九. MS MLPA Probe位置(缺失位置) 52 表十.各族群帶因者比例比較 53 表十一. Transmission of FMR1 allele to offspring 54 表十二.實驗方法比較 55 | - |
dc.language.iso | zh_TW | - |
dc.title | X染色體脆折症帶因者篩檢-台灣經驗 | zh_TW |
dc.title | Carrier Screening for Fragile X Syndrome in Taiwan | en |
dc.type | Thesis | - |
dc.date.schoolyear | 106-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.oralexamcommittee | 林芯?;蘇怡寧 | zh_TW |
dc.contributor.oralexamcommittee | Shin-Yu Lin;Yi-Ning Su | en |
dc.subject.keyword | X染色體脆折症,產前篩檢,遺傳諮詢, | zh_TW |
dc.subject.keyword | Fragile X syndrome,prenatal screening,genetic counseling, | en |
dc.relation.page | 55 | - |
dc.identifier.doi | 10.6342/NTU201803446 | - |
dc.rights.note | 未授權 | - |
dc.date.accepted | 2018-08-15 | - |
dc.contributor.author-college | 醫學院 | - |
dc.contributor.author-dept | 分子醫學研究所 | - |
dc.date.embargo-lift | 2023-10-09 | - |
顯示於系所單位: | 分子醫學研究所 |
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