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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 楊偉勛(Wei-Shiung Yang) | |
dc.contributor.author | Li-Chiao Yang | en |
dc.contributor.author | 楊麗巧 | zh_TW |
dc.date.accessioned | 2021-06-08T04:18:58Z | - |
dc.date.copyright | 2010-09-09 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-07-25 | |
dc.identifier.citation | 中文文獻
【1】吳哲宗:卡曼氏症候群患者(Kallmann Syndrome)在KAL-1 基因上突變的搜尋與探討—以台大醫院的病患為例.2009 【2】行政院衛生署台灣e院--罕見疾病 http://sp1.cto.doh.gov.tw/doctor/ 【3】財團法人罕見疾病基金會 http://www.tfrd.org.tw/ 【4】黃愛珠:『腎上腺腦白質退化症』的壓力因應.2006 英文文獻 【1】Catherine Dodé , Jean-Pierre: Kallmann syndrome. Hardelin European Journal of Human Genetics.2009; 17:139–146. 【2】Trarbach EB, Silveira LG, Latronico AC: Genetic insights into human isolated gonadotropin deficiency. Pituitary. 2007; 10(4):381-91. 【3】Pallais JC, Au M, Pitteloud N, Seminara S, Crowley WF Jr: Kallmann syndrome. GeneReviews -NCBI Bookshelf Update 2010 Apr 08. (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=kms) 【4】Kallmann FJ, Schönfeld WA, Barrera SE: The genetic aspects of primary eunuchoidism. Am J Ment Defic. 1943-1944; 48:203-236. 【5】synd/2549(http://www.whonamedit.com/synd.cfm/2549.html)at Who Named It? 【6】Fechner, A., Fong, S. & McGovern, P: A review of Kallmann Syndrome: Genetics, path physiology, and clinical management. Obstetrical and Gynecological Survey 2008; 63(3):189-194. 【7】Trarbach EB, Silveira LG, Latronico AC: Genetic insights into human isolated gonadotropin deficiency. Pituitary. 2007;10(4):381-91. 【8】Franco B, Guioli S, Pragliola A, Incerti B, Bardoni B, Tonlorenzi R, CarrozzoR, Maestrini E, Pieretti M, Taillon-Miller P, Brown CJ, Willard HF, LawrenceC, Persico MG, Camerino G, Ballabio A: A gene deleted in Kallmann’s Syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature.1991; 353:529–536 【9】Tsai PS, Gill JC. Mechanisms of disease: Insights into X-linked and autosomal-dominant Kallmann syndrome. Nat Clin Pract Endocrinol Metab. 2006 Mar; 2(3):160-71. 【10】Nelly Pitteloud, James S. Acierno, Jr., Astrid U. Meysing, Andrew A. Dwyer, Frances J. Hayes and William F. Crowley, Jr: Reversible Kallmann Syndrome, Delayed Puberty, and Isolated Anosmia Occurring in a Single Family with a Mutation in the Fibroblast Growth Factor Receptor 1 Gene. The Journal of Clinical Endocrinology & Metabolism.2009,90(3):1317-1322. 【11】Pitteloud N, Acierno JS Jr, Meysing A, Eliseenkova AV, Ma J, Ibrahimi OA, Metzger DL, Hayes FJ, Dwyer AA, Hughes VA, Yialamas M, Hall JE, Grant E, Mohammadi M, Crowley WF Jr: Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2006: Apr 18; 103(16):6281-6286 【12】Ford-Perriss M., Abud H., Murphy M: Fibroblast growth factors in the developing central nervous system. Clin. Exp. Pharmacol.Physiol.2001 (28):493–503. 【13】Dode C, Levilliers J, Dupont JM, De Paepe A, Le Du N, Soussi-Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pecheux C, Le Tessier D, Cruaud C, Delpech M, Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP: Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nature Genetics. 2003(33):463-465. 【14】Naoko Sato, Noriyuki Katsumata, Masayo Kagami, Tomonobu Hasegawa, Naoaki Hori, Setsuyo Kawakita, Shigeru Minowada, Aki Shimotsuka, Yoshimasa Shishiba, Masato Yokozawa, Toshiyuki Yasuda, Keisuke Nagasaki, Daiichiro Hasegawa, Yukihiro Hasegawa, Katsuhiko Tachibana, Yasuhiro Naiki, Reiko Horikawa, Toshiaki Tanaka and Tsutomu Ogata: Clinical Assessment and Mutation Analysis of Kallmann Syndrome 1 (KAL1) and Fibroblast Growth Factor Receptor 1 (FGFR1, or KAL2) in Five Families and 18 Sporadic Patients. 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Proc Natl Acad Sci U S A. 1992; 89:8190–8194. 【18】Franco B, Guioli S, Pragliola A, Incerti B, Bardoni B, Tonlorenzi R,Carrozzo R, Maestrini E, Pieretti M, Taillon-Miller P, Brown CJ,Willard HF, Lawrence CH, Persico MG, Camerino G, Ballabio A: A gene deleted in Kallmann’s syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature.1991; 353:529–536. 【19】Catherine Dode´, and Jean-Pierre Hardelin: Kallmann Syndrome. European Journal of Human Genetics. 2009; 17:139–146 【20】Sato N et al.: Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients. J Clin Endocrinol Metab. 2004; 89(3): 1079–1088. 【21】Izumi Y, Tastumi K, Okamoto S, Ogawa T, Hosokawa A, Matsuo T, Kato Y,Fukui H: Amino N 2001 Analysis of the KAL1 gene in 19 Japanese patients with Kallmann syndrome. Endocr J. 2001; 48:143–149. 【22】Hardelin JP, Levilliers J, Blanchard S, Carel JC, Leutenegger M, Pinard- Bertelletto JP, Bouloux P Petit C: Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome. Hum Mol Genet. 1993;2:373–377 【23】Maya-Nunez G, Zenteno JC, Ulloa-Aguirre A, Kofman-Alfaro S, Mendez JP: A recurrent missense mutation in the KAL gene in patients with X-linked Kallmann’s syndrome. J Clin Endocrinol Metab. 1998; 83:1650–1653 【24】Georgopoulos NA, Pralong FP, Seidman CE, Seidman JG, Crowley Jr WF, Vallejo M: Genetic heterogeneity evidenced by low incidence of KAL-1 gene mutations in sporadic cases of gonadotropin-releasing hormone deficiency. J Clin Endocrinol Metab. 1997; 82:213–217 【25】Oliveira LM, Seminara SB, Beranova M, Hayes FJ, Valkenburgh SB, Schipani E, Costa EM, Latronico AC, Crowley Jr WF, Vallejo M: The importance of autosomal genes in Kallmann syndrome: genotype-phenotype correlations and neuroendocrine characteristics. J Clin Endocrinol Metab.2001; 86: 1532–1538 【26】Ruta M, Burgess W, Givol D, Epstein J, Neiger N, Kaplow J, Crumley G, Dionne C, Jaye M, Schlessinger J: Receptor for acidic fibroblast growth factor is related to the tyrosine kinase encoded by the fms-like gene (FLG). Proc Natl Acad Sci USA 1989; 86:8722–8726. 【27】Carine Monnier, Catherine Dode´, Ludovic Fabre, Luis Teixeira, Gilles Labesse, Jean-Philippe Pin, Jean-Pierre Hardelin, and Philippe Rondard: PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity. Human Molecular Genetics. 2009; 18:75–81 【28】Leroy C, Fouveaut C, Leclercq S, Jacquemont S, Boullay HD, Lespinasse J, Delpech M, Dupont JM, Hardelin JP, Dodé C: Biallelic mutations in the prokineticin-2 gene in two sporadic cases of Kallmann syndrome. Eur J Hum Genet. 2008 Jul; 16(7):865-868. 【29】Nelly Pitteloud, Chengkang Zhang, Duarte Pignatelli, Jia-Da Li, Taneli Raivio, Lindsay W. Cole, Lacey Plummer, Elka E. Jacobson-Dickman, Pamela L. Mellon, Qun-Yong Zhou, and William F. Crowley, Jr: Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci USA. 2007 October 30; 104(44): 17447–17452. 【30】Kim HG, Kurth I, Lan F, Meliciani I, Wenzel W, Eom SH, Kang GB, Rosenberger G, Tekin M, Ozata M, Bick DP, Sherins RJ, Walker SL, Shi Y, Gusella JF, Layman LC: Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet. 2008; Oct; 83(4):511-519. 【31】Jongmans MC, van Ravenswaaij-Arts CM, Pitteloud N, Ogata T, Sato N, Claahsen-van der Grinten HL, van der Donk K, Seminara S, Bergman JE, Brunner HG, Crowley WF Jr, Hoefsloot LH: CHD7 mutations in patients initially diagnosed with Kallmann syndrome--the clinical overlap with CHARGE syndrome. Clin Genet. 2009; Jan; 75(1):65-71. 【32】Gemel J, Gorry M, Ehrlich GD, MacArthur CA: Structure and sequence of human FGF8. Genomics. 1996; Jul 1; 35(1):253-257. 【33】Dode´ C, Teixeira L, Levilliers J, Fouveaut C, Bouchard P, et al: Kallmann syndrome: Mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet. 2006; 2(10). 【34】Robert K, Semple and A, Kemal Topaloglu: The recent genetics of hypogonadotrophic hypogonadism – novel insights and new questions. Clinical Endocrinology (2010) 72, 427–435. 【35】Kallmann syndrome – Genetics Home Reference(http://ghr.nlm.nih.gov/condition=kallmannsyndrome) 【36】Hefner J, Csef H, Seufert J: Hypothalamic hypogonadism with anosmia (Kallmann's syndrome).Deutsche medizinische Wochenschrift. 2009;134(22): 1157-1160. 【37】Fechner, Adam MD, Fong, Shirley MD, McGovern, Peter MD: A Review of Kallmann Syndrome:Genetics, Pathophysiology, and Clinical Management. Obstetrical & Gynecological Survey.2008; 63 (3):189-194. 【38】Spitz IM. Isolated gonadotropin deficiency: a heterogenous syndrome. N Engl J Med 1974; 290:10. 【39】Yen SC, Jaffe RB, Barbieri RL. Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. 4th ed. Philadelphia: WB Saunders Company, 1999. 【40】Keye WR, Kelch RP, Niswender GD, et al. Quantitation of endogenous and exogenous gonadotropin releasing hormone by radioimmunoassay. J Clin Endocrinol Metab 1973; 36: 1263–1267. 【41】Doty RL, Shaman P, Dann M. The development of the University of Pennsylvania smell identification test. Physiol Behav 1984; 32:501–507. 【42】Klingmuller D, Duwes W, Krahe T, et al. Magnetic resonance imaging of the brain in patients with anosmia and hypothalamic hypogonadism (Kallmann’s syndrome). J Clin Endocrinol Metab 1987; 65:581–584. 【43】Truwitt CL, Barkovich AJ, Grumbach MM, et al. MR imaging of Kallmann syndrome, a genetic disorder of neuronal migration affecting the olfactory and genital systems. Am J Neuroradiol 1993; 14:827–838. 【44】Madan R, Sawlani V, Gupta S, et al. MRI findings in Kallmann syndrome. Neurol India 2004; 52:501–503. 【45】Birnbacher R, Wandl-Vergesslich K, Frisch H. Diagnosis of X-recessive Kallmann syndrome in early infancy. Evidence of hypoplastic rhinencephalon. Eur J Pediatr 1994; 153:245–247. 【46】Robert K. Semple and A. Kemal Topaloglu:The recent genetics of hypogonadotrophic hypogonadism – novel insights and new questions. Clinical Endocrinology. 2010; 72:427–435. 【47】Bhagavath B, Podolsky RH, Ozata M, Bolu E, Bick DP, Kulharya A,Sherins RJ, Layman LC: Clinical and molecular characterization of a large sample of patients with hypogonadotropic hypogonadism. Fertil Steril 2006; 85:706–713. 【48】Ericka Barbosa Trarbach, Milena Gurgel Teles, Elaine Maria Frade Costa, Ana Paula Abreu, Heraldo Mendes Garmes, Gil Guerra-Junior, Maria Tereza Matias Baptista, Margaret de Castro, Berenice Bilharinho Mendonca and Ana Claudia Latronico:Screening of autosomal gene deletions in patients with hypogonadotropic hypogonadism using multiplex ligationdependent probe amplification: detection of a hemizygosis for the fibroblast growth factor receptor 1.Clinical Endocrinology. 2010; 72(3):371–376. 【49】Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G: Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 2002; 30:e57. 【50】Hogervorst FB, Nederlof PM, Gille JJ, McElgunn CJ, Grippeling M, Pruntel R, Regnerus R, van Welsem T, van Spaendonk R, Menko FH et al: Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method. Cancer Res. 2003; 63:1449–1453. 【51】Zofia K.Z. Gajdosa,Katherine D. Henderson, Joel N. Hirschhorn and Mark R. Palmert: Genetic determinants of pubertal timing in the general population.Molecular and Cellular Endocrinology.2010;324(1-2, 5):21-29. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22488 | - |
dc.description.abstract | 卡爾曼氏症候群(Kallmann Syndrome)是X染色體及體染色體上基因缺陷所造成的遺傳疾病,主要是性腺激素功能低下與性腺功能低下伴隨嗅覺缺失或嗅覺低下。卡爾曼氏症候群屬於極為罕見的疾病,發生率約為1/8,000個出生男嬰與1/40,000個出生女嬰。目前已知卡爾曼氏症候群分成六個基因型:KAL1、KAL 2、KAL 3、KAL 4、KAL 5和KAL 6。其中KAL 1、KAL 2、KAL 3、KAL 4這四型在卡爾曼氏症候群中約佔30%。文獻報告指出,卡爾曼氏症候群患者可藉由早期臨床介入,如由賀爾蒙替代療法來改善病徵。
本研究中收集了一位女性、七位男性,共計八名疑似為卡爾曼氏症候群病人。我們利用聚合酶連鎖反應技術,試圖從中找出關於卡爾曼氏症候群第二型、第三型及第四型基因的突變點位。檢測結果發現個案均無第二型、第三型及第四型的突變點,而案例中的一名七歲男童之前已被證實KAL-1 geene發生突變。建議下位研究者可以選擇其他疾病候選基因或除了點突變以外的技術來進一步探索;甚至,精確的臨床診斷對卡爾曼氏症候群是一個重要的研究意義。 | zh_TW |
dc.description.abstract | Kallmann Syndrome (KS), an inherited syndrome with gene defects carried by the X chromosome and autosome chromosomes, characterized by hypogonadotropic hypogonadism with anosmia or hypoosmia. KS is a rare syndrome with an incidence of 1/8000 in male babies and 1/40000 in female babies. There are six KS genes identified:KAL-1, KAL-2, KAL-3, KAL-4, KAL-5 and KAL-6. The first four types, KAL-1, KAL-2, KAL-3 and KAL-4, almost take up 30% of KS cases. With the advancement in the KS research, the clinical manifestations of KS patients can be improved by early clinical interventions, such as the hormone replacement therapy(HRT).
In this study, we collected samples from one female, and seven males who are suspected to have KS. One boy was previously identified to have mutation in KAL-1 gene. In this study, I screened mutation of KAL-2, KAL-3, and KAL-4 of KS from these samples by direct PCR-sequencing. We did not find any mutation among them. Further exploration of the other candidate genes or the use of the other genotyping technologies for mutations other than point mutation should be employed in the future. A precise clinical protocol for future genetic study is also important to improve the quality of this genetic study. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T04:18:58Z (GMT). No. of bitstreams: 1 ntu-99-P97448013-1.pdf: 5609232 bytes, checksum: 6fbef0070f98141440bad99211c130f5 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 書名頁 .................................................. Ⅰ
口試審定書 .............................................. Ⅱ 中文摘要 ................................................ Ⅲ 英文摘要 ................................................ Ⅳ 誌謝 .................................................... Ⅴ 目錄 .................................................... Ⅵ 表目錄 .................................................. Ⅷ 圖目錄 .................................................. Ⅸ 第壹章 緒論.............................................. 1 第一節 研究背景與動機.................................... 1 第二節 研究目的.......................................... 3 第三節 研究範圍與限制.................................... 4 第貳章 相關文獻探討...................................... 5 第一節 卡爾曼氏症候群(Kallmann Syndrome;KS)的簡介..... 5 一、Kallmann Syndrome 1(KS1)........................... 6 二、Kallmann Syndrome 2(KS2)........................... 6 三、Kallmann Syndrome 3(KS3)........................... 7 四、Kallmann Syndrome 4(KS4)........................... 7 五、Kallmann Syndrome 5(KS5)........................... 8 六、Kallmann Syndrome 6(KS6)........................... 9 第二節 卡爾曼氏症候群(Kallmann Syndrome;KS)的臨床症狀. 9 第三節 卡爾曼氏症候群(Kallmann Syndrome;KS)的診斷.....13 第四節 卡爾曼氏症候群(Kallmann Syndrome;KS)的治療及預後15 第參章 實驗材料與研究方法................................16 第一節 實驗材料..........................................16 一、KS病人來源...........................................16 二、引子設計(Primer design)............................16 三、實驗所需的儀器和試劑.................................17 第二節 研究方法 – 共同的部份............................18 一、人體DNA的萃取(Genomic DNA Extraction)..............18 二、聚合酶連鎖反應(Polymerase Chain Reaction;PCR).....18 三、洋菜凝膠電泳 (Agarose gel electrophoresis).........19 四、自動化定序分析與結果確認.............................20 第三節 研究步驟 – 實做的部份............................21 一、人體DNA的萃取(Genomic DNA Extraction)..............21 二、聚合酶連鎖反應(Polymerase Chain Reaction;PCR).....22 三、洋菜膠體之配製(Agarose gel preparation)............23 四、洋菜凝膠電泳(Agarose gel electrophoresis)..........23 五、基因定序分析比對及結果確認...........................24 第肆章 研究結果與分析....................................25 第一節 家族及個案資料分析................................25 第二節 基因序列檢定結果..................................33 第伍章 討論與建議........................................36 第一節 結果分析與討論....................................36 第二節 未來研究方向建議..................................40 參考文獻.................................................41 附錄.....................................................47 | |
dc.language.iso | zh-TW | |
dc.title | 卡爾曼氏症候群病人個案的分子遺傳學研究 | zh_TW |
dc.title | The study of Molecular Genetics of clients from patients with Kallmann Syndrome | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 蔡文友(Tsai ,Wen-Yu),蘇怡寧(SU, YI-NING) | |
dc.subject.keyword | 卡爾曼氏症候群,下視丘-腦下垂腺軸,促性腺激素分泌不足的低性腺功能症,嗅覺喪失,青春期遲緩, | zh_TW |
dc.subject.keyword | Kallmann Syndrome,Hypothalamic-Pituitary Axis,Hypogonadotropic,Hypogonadism(HH),Anosmia,Delayed Puberty, | en |
dc.relation.page | 55 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2010-07-26 | |
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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