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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 楊偉勛(Wei-Shiung Yang) | |
| dc.contributor.author | Hsin-Yao Chen | en |
| dc.contributor.author | 陳心窈 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:23:34Z | - |
| dc.date.available | 2018-09-24 | |
| dc.date.copyright | 2013-09-24 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-16 | |
| dc.identifier.citation | 1. Pierson, M. & Leheup, B. [Bourneville's tuberous sclerosis]. J Genet Hum 36, 181-99 (1988).
2. Rodrigues, D.A., Gomes, C.M. & Costa, I.M. Tuberous sclerosis complex. An Bras Dermatol 87, 184-96 (2012). 3. Grant, V. Tuberous sclerosis (Bourneville's disease). J Ophthalmic Nurs Technol 8, 143-7 (1989). 4. Storm, K., Krag-Olsen, B. & Wolthers, O.D. [Tuberous sclerosis]. Ugeskr Laeger 151, 2962-5 (1989). 5. Cheadle, J.P., Reeve, M.P., Sampson, J.R. & Kwiatkowski, D.J. Molecular genetic advances in tuberous sclerosis. Hum Genet 107, 97-114 (2000). 6. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75, 1305-15 (1993). 7. van Slegtenhorst, M. et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 277, 805-8 (1997). 8. Fernandez-Guarino, M., Boixeda, P., Anaya, M.J., Belmar, P. & Jaen, P. [Clinical findings in 67 patients with tuberous sclerosis]. Actas Dermosifiliogr 100, 596-601 (2009). 9. Schwartz, R.A., Fernandez, G., Kotulska, K. & Jozwiak, S. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol 57, 189-202 (2007). 10. Harrison, J.E. & Bolton, P.F. Annotation: tuberous sclerosis. J Child Psychol Psychiatry 38, 603-14 (1997). 11. Gomez, M.R. History of the tuberous sclerosis complex. Brain Dev 17 Suppl, 55-7 (1995). 12. Lendvay, T.S. & Marshall, F.F. The tuberous sclerosis complex and its highly variable manifestations. J Urol 169, 1635-42 (2003). 13. Bundey, S. & Evans, K. Tuberous sclerosis: a genetic study. J Neurol Neurosurg Psychiatry 32, 591-603 (1969). 14. Fryer, A.E. et al. Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet 1, 659-61 (1987). 15. Roach, E.S. & Sparagana, S.P. Diagnosis of tuberous sclerosis complex. J Child Neurol 19, 643-9 (2004). 16. Osborne, J.P., Fryer, A. & Webb, D. Epidemiology of tuberous sclerosis. Ann N Y Acad Sci 615, 125-7 (1991). 17. Pulsifer, M.B., Winterkorn, E.B. & Thiele, E.A. Psychological profile of adults with tuberous sclerosis complex. Epilepsy Behav 10, 402-6 (2007). 18. Manohara, D. Primary care management of tuberous sclerosis complex in children. J Am Acad Nurse Pract 24, 391-9 (2012). 19. Leung, A.K. & Robson, W.L. Tuberous sclerosis complex: a review. J Pediatr Health Care 21, 108-14 (2007). 20. Borkowska, J., Schwartz, R.A., Kotulska, K. & Jozwiak, S. Tuberous sclerosis complex: tumors and tumorigenesis. Int J Dermatol 50, 13-20 (2011). 21. Bader, R.S. et al. Fetal rhabdomyoma: prenatal diagnosis, clinical outcome, and incidence of associated tuberous sclerosis complex. J Pediatr 143, 620-4 (2003). 22. Baskin, H.J., Jr. The pathogenesis and imaging of the tuberous sclerosis complex. Pediatr Radiol 38, 936-52 (2008). 23. Rouviere, O., Nivet, H., Grenier, N., Zini, L. & Lechevallier, E. Kidney damage due to tuberous sclerosis complex: management recommendations. Diagn Interv Imaging 94, 225-37 (2013). 24. Kitano, Y. et al. Renal angiomyolipoma in Japanese tuberous sclerosis patients. J Pediatr Surg 39, 1784-6 (2004). 25. Dixon, B.P., Hulbert, J.C. & Bissler, J.J. Tuberous sclerosis complex renal disease. Nephron Exp Nephrol 118, e15-20 (2011). 26. Staley, B.A. et al. Self-injurious behavior and tuberous sclerosis complex: frequency and possible associations in a population of 257 patients. Epilepsy Behav 13, 650-3 (2008). 27. Han, J.M. & Sahin, M. TSC1/TSC2 signaling in the CNS. FEBS Lett 585, 973-80 (2011). 28. Smalley, S.L. Autism and tuberous sclerosis. J Autism Dev Disord 28, 407-14 (1998). 29. Evans, L.T., Morse, R. & Roberts, D.W. Epilepsy surgery in tuberous sclerosis: a review. Neurosurg Focus 32, E5 (2012). 30. Badawi, R.A. & Geddes, D.M. Exertional haemoptysis: LAM and TSC. Thorax 58, 460 (2003). 31. Sparling, J.D., Hong, C.H., Brahim, J.S., Moss, J. & Darling, T.N. Oral findings in 58 adults with tuberous sclerosis complex. J Am Acad Dermatol 56, 786-90 (2007). 32. Osborne, J.P. Diagnosis of tuberous sclerosis. Arch Dis Child 63, 1423-5 (1988). 33. Hyman, M.H. & Whittemore, V.H. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol 57, 662-5 (2000). 34. Au, K.S., Ward, C.H. & Northrup, H. Tuberous sclerosis complex: disease modifiers and treatments. Curr Opin Pediatr 20, 628-33 (2008). 35. Perek-Polnik, M., Jozwiak, S., Jurkiewicz, E., Perek, D. & Kotulska, K. Effective everolimus treatment of inoperable, life-threatening subependymal giant cell astrocytoma and intractable epilepsy in a patient with tuberous sclerosis complex. Eur J Paediatr Neurol 16, 83-5 (2012). 36. Jang, M.A. et al. Identification of TSC1 and TSC2 mutations in Korean patients with tuberous sclerosis complex. Pediatr Neurol 46, 222-4 (2012). 37. Lamb, R.F. et al. The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho. Nat Cell Biol 2, 281-7 (2000). 38. Imai, K. et al. Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes. Gene 222, 287-95 (1998). 39. Hodges, A.K. et al. Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin. Hum Mol Genet 10, 2899-905 (2001). 40. Benvenuto, G. et al. The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination. Oncogene 19, 6306-16 (2000). 41. van Slegtenhorst, M. et al. Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet 7, 1053-7 (1998). 42. Kwiatkowski, D.J. Tuberous sclerosis: from tubers to mTOR. Ann Hum Genet 67, 87-96 (2003). 43. Inoki, K., Li, Y., Zhu, T., Wu, J. & Guan, K.L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4, 648-57 (2002). 44. Hay, N. & Sonenberg, N. Upstream and downstream of mTOR. Genes Dev 18, 1926-45 (2004). 45. Potter, C.J., Pedraza, L.G., Huang, H. & Xu, T. The tuberous sclerosis complex (TSC) pathway and mechanism of size control. Biochem Soc Trans 31, 584-6 (2003). 46. Nellist, M. et al. Distinct effects of single amino-acid changes to tuberin on the function of the tuberin-hamartin complex. Eur J Hum Genet 13, 59-68 (2005). 47. Ozcan, U. et al. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell 29, 541-51 (2008). 48. Jones, A.C. et al. Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis. Am J Hum Genet 64, 1305-15 (1999). 49. Kozlowski, P. et al. Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Hum Genet 121, 389-400 (2007). 50. Sancak, O. et al. Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype--phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex. Eur J Hum Genet 13, 731-41 (2005). 51. Dabora, S.L. et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet 68, 64-80 (2001). 52. Torra, R. et al. Facilitated diagnosis of the contiguous gene syndrome: tuberous sclerosis and polycystic kidneys by means of haplotype studies. Am J Kidney Dis 31, 1038-43 (1998). 53. Niida, Y. et al. Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis. Hum Mutat 14, 412-22 (1999). 54. Mayer, K., Ballhausen, W. & Rott, H.D. Mutation screening of the entire coding regions of the TSC1 and the TSC2 gene with the protein truncation test (PTT) identifies frequent splicing defects. Hum Mutat 14, 401-11 (1999). 55. Benit, P. et al. Denaturing high-performance liquid chromatography (DHPLC)-based prenatal diagnosis for tuberous sclerosis. Prenat Diagn 21, 279-83 (2001). 56. Guldberg, P. & Guttler, F. A simple method for identification of point mutations using denaturing gradient gel electrophoresis. Nucleic Acids Res 21, 2261-2 (1993). 57. Moyret, C. et al. Relative efficiency of denaturing gradient gel electrophoresis and single strand conformation polymorphism in the detection of mutations in exons 5 to 8 of the p53 gene. Oncogene 9, 1739-43 (1994). 58. Padma Priya, T. & Dalal, A.B. Tuberous sclerosis: diagnosis and prenatal diagnosis by MLPA. Indian J Pediatr 79, 1366-9 (2012). 59. Willis, A.S., van den Veyver, I. & Eng, C.M. Multiplex ligation-dependent probe amplification (MLPA) and prenatal diagnosis. Prenat Diagn 32, 315-20 (2012). 60. Rendtorff, N.D. et al. Analysis of 65 tuberous sclerosis complex (TSC) patients by TSC2 DGGE, TSC1/TSC2 MLPA, and TSC1 long-range PCR sequencing, and report of 28 novel mutations. Hum Mutat 26, 374-83 (2005). 61. Liu, L. et al. Comparison of next-generation sequencing systems. J Biomed Biotechnol 2012, 251364 (2012). 62. Sanger, F., Nicklen, S. & Coulson, A.R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 74, 5463-7 (1977). 63. Collins, F.S., Morgan, M. & Patrinos, A. The Human Genome Project: lessons from large-scale biology. Science 300, 286-90 (2003). 64. Shendure, J. & Ji, H. Next-generation DNA sequencing. Nat Biotechnol 26, 1135-45 (2008). 65. Zhang, J., Chiodini, R., Badr, A. & Zhang, G. The impact of next-generation sequencing on genomics. J Genet Genomics 38, 95-109 (2011). 66. Kriseman, J., Busick, C., Szelinger, S. & Dinu, V. BING: biomedical informatics pipeline for Next Generation Sequencing. J Biomed Inform 43, 428-34 (2010). 67. Li, W. et al. [Mutation screening and prenatal diagnosis of tuberous sclerosis complex]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 28, 361-6 (2011). 68. Schouten, J.P. et al. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30, e57 (2002). 69. den Dunnen, J.T. & White, S.J. MLPA and MAPH: sensitive detection of deletions and duplications. Curr Protoc Hum Genet Chapter 7, Unit 7 14 (2006). 70. Gouas, L., Goumy, C., Veronese, L., Tchirkov, A. & Vago, P. Gene dosage methods as diagnostic tools for the identification of chromosome abnormalities. Pathol Biol (Paris) 56, 345-53 (2008). 71. Glynn, A., Saya, S. & Halliday, J. Use and non-use of genetic counseling after diagnosis of a birth defect. Am J Med Genet A 158A, 559-66 (2012). 72. Biesecker, B.B. Goals of genetic counseling. Clin Genet 60, 323-30 (2001). 73. Biesecker, B.B. & Peters, K.F. Process studies in genetic counseling: peering into the black box. Am J Med Genet 106, 191-8 (2001). 74. Kessler, S. 12. The genetic counselor as psychotherapist. Birth Defects Orig Artic Ser 15, 187-200 (1979). 75. Longa, L. et al. TSC1 and TSC2 deletions differ in size, preference for recombinatorial sequences, and location within the gene. Hum Genet 108, 156-66 (2001). 76. Lander, E.S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860-921 (2001). 77. Batzer, M.A. et al. Standardized nomenclature for Alu repeats. J Mol Evol 42, 3-6 (1996). 78. Kaer, K. & Speek, M. Intronic retroelements: Not just 'speed bumps' for RNA polymerase II. Mob Genet Elements 2, 154-157 (2012). 79. Kapitonov, V. & Jurka, J. The age of Alu subfamilies. J Mol Evol 42, 59-65 (1996). 80. Price, A.L., Eskin, E. & Pevzner, P.A. Whole-genome analysis of Alu repeat elements reveals complex evolutionary history. Genome Res 14, 2245-52 (2004). 81. Abdurashitov, M.A., Tomilov, V.N., Chernukhin, V.A. & Degtyarev, S. A physical map of human Alu repeats cleavage by restriction endonucleases. BMC Genomics 9, 305 (2008). 82. Stenger, J.E. et al. Biased distribution of inverted and direct Alus in the human genome: implications for insertion, exclusion, and genome stability. Genome Res 11, 12-27 (2001). 83. Deininger, P.L. & Batzer, M.A. Alu repeats and human disease. Mol Genet Metab 67, 183-93 (1999). 84. Wagstaff, B.J. et al. Rescuing Alu: recovery of new inserts shows LINE-1 preserves Alu activity through A-tail expansion. PLoS Genet 8, e1002842 (2012). 85. Sorek, R. The birth of new exons: mechanisms and evolutionary consequences. RNA 13, 1603-8 (2007). 86. Belancio, V.P., Hedges, D.J. & Deininger, P. Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res 18, 343-58 (2008). 87. Gallus, G.N. et al. Alu-element insertion in an OPA1 intron sequence associated with autosomal dominant optic atrophy. Mol Vis 16, 178-83 (2010). 88. Okubo, M. et al. A novel complex deletion-insertion mutation mediated by Alu repetitive elements leads to lipoprotein lipase deficiency. Mol Genet Metab 92, 229-33 (2007). 89. Kaer, K. & Speek, M. Retroelements in human disease. Gene 518, 231-41 (2013). 90. Luo, D.X., Li, K., He, S.Y. & Liao, D.F. [Alu family and its biological significance]. Yi Chuan 27, 284-8 (2005). 91. Ullu, E. & Weiner, A.M. Human genes and pseudogenes for the 7SL RNA component of signal recognition particle. EMBO J 3, 3303-10 (1984). 92. Shankar, R., Grover, D., Brahmachari, S.K. & Mukerji, M. Evolution and distribution of RNA polymerase II regulatory sites from RNA polymerase III dependant mobile Alu elements. BMC Evol Biol 4, 37 (2004). 93. Fuhrman, S.A., Deininger, P.L., LaPorte, P., Friedmann, T. & Geiduschek, E.P. Analysis of transcription of the human Alu family ubiquitous repeating element by eukaryotic RNA polymerase III. Nucleic Acids Res 9, 6439-56 (1981). 94. Sinnett, D., Richer, C., Deragon, J.M. & Labuda, D. Alu RNA secondary structure consists of two independent 7 SL RNA-like folding units. J Biol Chem 266, 8675-8 (1991). 95. Oler, A.J. et al. Alu expression in human cell lines and their retrotranspositional potential. Mob DNA 3, 11 (2012). 96. Styles, P. & Brookfield, J.F. Source gene composition and gene conversion of the AluYh and AluYi lineages of retrotransposons. BMC Evol Biol 9, 102 (2009). 97. Batzer, M.A. & Deininger, P.L. Alu repeats and human genomic diversity. Nat Rev Genet 3, 370-9 (2002). 98. Batzer, M.A. et al. African origin of human-specific polymorphic Alu insertions. Proc Natl Acad Sci U S A 91, 12288-92 (1994). 99. Bennett, E.A. et al. Active Alu retrotransposons in the human genome. Genome Res 18, 1875-83 (2008). 100. Okada, N., Hamada, M., Ogiwara, I. & Ohshima, K. SINEs and LINEs share common 3' sequences: a review. Gene 205, 229-43 (1997). 101. Boissinot, S., Chevret, P. & Furano, A.V. L1 (LINE-1) retrotransposon evolution and amplification in recent human history. Mol Biol Evol 17, 915-28 (2000). 102. Ponicsan, S.L., Kugel, J.F. & Goodrich, J.A. Genomic gems: SINE RNAs regulate mRNA production. Curr Opin Genet Dev 20, 149-55 (2010). 103. Ostertag, E.M. & Kazazian, H.H., Jr. Biology of mammalian L1 retrotransposons. Annu Rev Genet 35, 501-38 (2001). 104. Carnell, A.N. & Goodman, J.I. The long (LINEs) and the short (SINEs) of it: altered methylation as a precursor to toxicity. Toxicol Sci 75, 229-35 (2003). 105. Streva, V.A., Faber, Z.J. & Deininger, P.L. LINE-1 and Alu retrotransposition exhibit clonal variation. Mob DNA 4, 16 (2013). 106. Kramerov, D.A. & Vassetzky, N.S. SINEs. Wiley Interdiscip Rev RNA 2, 772-86 (2011). 107. Loeb, D.D. et al. The sequence of a large L1Md element reveals a tandemly repeated 5' end and several features found in retrotransposons. Mol Cell Biol 6, 168-82 (1986). 108. Alisch, R.S., Garcia-Perez, J.L., Muotri, A.R., Gage, F.H. & Moran, J.V. Unconventional translation of mammalian LINE-1 retrotransposons. Genes Dev 20, 210-24 (2006). 109. Kolosha, V.O. & Martin, S.L. In vitro properties of the first ORF protein from mouse LINE-1 support its role in ribonucleoprotein particle formation during retrotransposition. Proc Natl Acad Sci U S A 94, 10155-60 (1997). 110. Weiner, A.M. SINEs and LINEs: the art of biting the hand that feeds you. Curr Opin Cell Biol 14, 343-50 (2002). 111. Sirivanichsuntorn, P. et al. LINE-1 and Alu hypomethylation in mucoepidermoid carcinoma. BMC Clin Pathol 13, 10 (2013). 112. Aoki, Y. et al. Genomic vulnerability to LINE-1 hypomethylation is a potential determinant of the clinicogenetic features of multiple myeloma. Genome Med 4, 101 (2012). 113. Choi, I.S. et al. Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors). Mod Pathol 20, 802-10 (2007). 114. Galeeva, N.M., Nenasheva, S.A., Kleimenova, I.S. & Poliakov, A.V. [Novel large deletion c.22-1320_633+1224del in the CYB5R3 gene from patients with hereditary methemoglobinemia]. Genetika 48, 1336-46 (2012). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60617 | - |
| dc.description.abstract | 腫瘤抑制基因中的 TSC1 (MIM#605284)和 TSC2 (MIM#191092)在人類生殖系發生突變時會引起結節硬化症(TSC, MIM#191100)，是屬於體染色體顯性遺傳疾病，並且在身體的多個器官有錯構瘤的產生，包括腦(結節、室管膜下結節和室管膜下巨細胞星形細胞瘤)、皮膚(面部血管纖維瘤和鯊魚斑)、心臟(橫紋肌瘤)、肺(淋巴管肌瘤病)、視網膜(星狀細胞缺陷瘤)和腎臟(血管平滑肌脂肪瘤)。結節硬化症發生率為1/6000~1/10000。大約有2/3的患者屬於散發型，沒有家族遺傳病史，是因為TSC1或TSC2 基因上發生新的突變，或者是父或母親性腺有鑲嵌體影響所引起。
TSC1 和TSC2 基因產物分別為hamartin和 tuberin，在蛋白質複合體的功能，以調節細胞訊號傳遞並且對於調節細胞生長，遷移和增殖是非常重要的。大多數的TSC1和TSC2為點突變和小的插入/缺失。 本次研究是將台大醫院結節硬化整合門診病友所提供的血液，53個家族中共62位結節硬化症患者，其中包括 proband 53位，47位有明確診斷的TSC患者及6位可能是TSC患者。這些患者在第一輪的次世代序列(NGS)的實驗和數據分析中，未找出引起變致病變異點或是小的插入或是缺失，本次實驗除了更詳細分析NGS的結果，並且使用多重連接探針擴增（MLPA）技術，針對大的缺失和/或插入進行基因變異篩檢。結果發現在其中1個TSC患者 TSC2 基因發現第16外顯子到第29個外顯子有大片段的缺失，其斷點兩端皆為Alu Y elemen，並且由Sanger定序法證實；而在另1個TSC患者，我們發現不論是在MLPA 或是NGS 中TSC2基因外顯子1的信號雖然皆表現低落，然而卻無法以 Sanger 定序法確認突變。最後我們的結論是NGS和MLPA對於檢測TSC患者的大片段缺失或是插入都屬於十分良好的檢測工具。 | zh_TW |
| dc.description.abstract | In human, germ-line mutations of the TSC1 (MIM#605284) or TSC2 (MIM#191092) tumor suppressor genes cause tuberous sclerosis complex (TSC, MIM#191100), an autosomal dominant disease in which hamartomas and/or hamartias are found in multiple organ systems, including brain (tubers, subependymal nodules and subependymal giant cell astrocytomas), skin (facial angiofibromas, hypomelanotic macules and shagreen patches), heart (cardiac rhabdomyomas), lungs (Lymphangioleiomyomatosis), retina (astrocytic hematoma), and kidney (angiomyolipomas). The prevalence of TSC is estimated as high as 1/6000~1/10000. About two-thirds of TSC patients are sporadic cases with no family history, and appear to represent new mutation occurring in either TSC1 or TSC2, or are transmitted from parents of gonadal mosaicism.
The TSC1 and TSC2 gene products (hamartin and tuberin) function in a protein complex to modulate cell signaling pathways that are important for regulation of cell growth, migration and proliferation. Point mutations and small insertions/deletions (indels) account for most TSC1 and TSC2 mutations. This study was carried out at the Joint TSC Clinics of National Taiwan University Hospital. We collected blood samples from 62 TSC patients in 53 pedigrees. Among the 53 probands, 47 individuals had definite diagnosis of TSC, and 6 individuals had possible diagnosis. For those patients that we did not detect causative substitutions or small indels in the first round of next-generation sequencing (NGS) experiments and data analyses, we performed further analyses of the NGS data and also conducted new experiments using the multiplex ligation-dependent probe amplification (MLPA) technology, aiming at identification of large deletions and/or insertions. We found a large deletion spanning exon 16 and exon 29 of the TSC2 gene in one TSC patient and mapped both breakpoints of the deletion to Alu Y elements. The findings were confirmed by Sanger sequencing. In another TSC patient, we found reduced signal at exon 1 of the TSC2 gene by data from both NGS and MLPA; however, we could not confirm this mutation by Sanger sequence yet. We conclude that NGS and MLPA are powerful tools to detect large deletions/insertions for TSC patients. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:23:34Z (GMT). No. of bitstreams: 1 ntu-102-P00448009-1.pdf: 7668886 bytes, checksum: 16ed1e8c042cc25804899791c1127683 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 口試委員會審定書 #
誌謝 II 目錄 III 英文縮寫 VI 中文摘要 VIII ABSTRACT X 第一章研究背景與動機 1 1.1 結節硬化症的簡介 1 1.2結節硬化症臨床特徵與診斷 4 1.2.1結節硬化症的臨床特徵 5 1.2.1.1皮膚. 5 1.2.1.2眼睛 6 1.2.1.3心臟 6 1.2.1.4腎臟 7 1.2.1.5神經系統 8 1.2.1.6血管 9 1.2.1.7肺部 9 1.2.1.8 口腔 9 1.2.1.9其他系統 10 1.3.臨床診斷和篩檢 10 1.3.1主要指標(Major Criteria) 11 1.3.2次要標準(Minor Criteria) 12 1.4治療 13 1.5結節硬化症的病因學 14 1.5.1 TSC 基因和功能 14 1.5.2 TSC分子檢測方式 17 1.6遺傳諮詢 24 1.7研究動機 27 第二章 研究方法 28 2.1.實驗儀器及器材 28 2.2藥品與材料 28 2.3研究方法及步驟. 29 2.3.1 TSC病人來源29 2.3.2 檢體收集 30 2.4 MLPA方法 30 2.4.1 MLAP試劑 30 2.4.2MLPA方法 32 2.5.3MLPA計算結果 33 2.5聚合酶連鎖反應原理與方法 34 2.6引子設計 35 2.7.1 PCR試劑 36 2.7.2 PCR條件 36 2.7 DNA定序 36 2.9諮詢個案 37 第三章研究結果 45 第四章 討論 50 第五章結論 60 REFERENCES 61 | |
| dc.language.iso | zh-TW | |
| dc.subject | 結節硬化症 | zh_TW |
| dc.subject | 體染色體顯性遺傳 | zh_TW |
| dc.subject | 基因檢測 | zh_TW |
| dc.subject | 次世代序列 | zh_TW |
| dc.subject | MLPA | zh_TW |
| dc.subject | MLPA | en |
| dc.subject | Tuberous sclerosis complex (TSC) | en |
| dc.subject | autosomal dominant disease | en |
| dc.subject | Genetic test | en |
| dc.subject | Next generation sequencing (NGS) | en |
| dc.title | 大片段缺失或插入所造成結節硬化症之基因診斷 | zh_TW |
| dc.title | Detection of large deletion(s) or insertion(s) responsible for tuberous sclerosis complex (TSC) | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 陳沛隆(Pei-Lung Chen) | |
| dc.contributor.oralexamcommittee | 謝豐舟 | |
| dc.subject.keyword | 結節硬化症,體染色體顯性遺傳,基因檢測,次世代序列,MLPA, | zh_TW |
| dc.subject.keyword | Tuberous sclerosis complex (TSC),autosomal dominant disease,Genetic test,Next generation sequencing (NGS),MLPA, | en |
| dc.relation.page | 68 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-16 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| Appears in Collections: | 分子醫學研究所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| ntu-102-1.pdf Restricted Access | 7.49 MB | Adobe PDF |
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