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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蘇怡寧(Yi-Ning Su) | |
| dc.contributor.author | Li-Yun Tseng | en |
| dc.contributor.author | 曾黎雲 | zh_TW |
| dc.date.accessioned | 2021-06-15T00:26:32Z | - |
| dc.date.available | 2010-02-17 | |
| dc.date.copyright | 2009-02-17 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-01-22 | |
| dc.identifier.citation | 1. Wright KW, Speiegel PH, Thompson LS. (2006). Handbook of pediatric neuro-ophthalmology (pp. 289-319). Chicago, IL: Springer.
2. Traboulsi EI. (1998). Genetic diseases of the eye (pp. 513-529). New York: Oxford. 3. Self J, Lotery A. (2007). A review of the molecular genetics of congenital idiopathic nystagmus (CIN). Semin Ophthalmo, 28, 187-191. 4. Self J, Lotery A. (2006).The molecular genetics of congenital idiopathic nystagmus. Semin Ophthalmo, 21, 87-90. 5. Hertle RW. (2008). Nystagmus in infancy and childhood. Semin Ophthalmo, 23, 307-317. 6. Tusa RJ. (1999).Nystagmus: diagnostic and therapeutic strategies. Semin Ophthalmo, 14(2), 65-73. 7. 褚仁遠、張琳（民國94年）。眼病學（頁267-268）。台北市：宏欣文化。 8. Leigh RJ, Khanna S. (2006). What can acquired nystagmus tell us about congenital forms of nystagmus? Semin Ophthalmo, 21(2), 83-86. 9. Pattion MA, Jeffery S, Lee n, Hogg C.(1993). Congenital nystagmus cosegregating with a balanced 7;15 translocation. J Mde Genet, 30, 526-528. 10. Kerrison JB, Arnould VJ, Barmada MM, Koenekoop K, Schmeckpeper BJ, Maumenee IH. (1996). A gene for autosomal dominant congenital nystagmus localizes to 6p12. Genomics, 33, 523-526. 11. Kerrison JB, Koenekoop RK, Arnould VJ, Zee D, Maumenee IH. (1998). Clinical features of autosomal dominant congenital nystagmus linked to chromosome 6p12. Am J Ophthalmol, 125, 64-70. 12. Linnankivi T, Tienari P, Somer M, Kähkönen M, Lönnqvist T, Valanne L, Pihko H. (2006). 18q deletions: clinical, molecular, and brain MRI findings of 14 individuals. Am J Med Genet A, 140, 331-339. 13. Klein C, Fieregge P, Heide W, Kemper B, Hagedorn-Greiwe M, Hagenah J, Vollmer C & et al. (1998). Exclusion of chromosome regions 6p12 and 15q11, but not chromosome region 7p11, in a German family with autosomal dominant congenital nystagmus. Genomics, 54, 176-177. 14. Hoffmann S, Becker A, Hoerle S, Metz A, Oertel WH, Sommer N, Hemmer B. (2004). Autosomal dominant congenital nystagmus is not linked to 6p12, 7p11, and 15q11 in a German family. Am J Ophthalmol, 138(3), 439-443. 15. Oetting WS, Armstrong CM, Holleschau AM, DeWan AT, Summers CG. (2000). Evidence for genetic heterogeneity in families with congenital motor nystagmus (CN). Ophthalmic Genet, 21(4), 227-233. 16. Kerrison JB, Vagefi MR, Barmada MM, Maumenee IH. (1999). Congenital motor nystagmus linked to Xq26-q27. Am J Hum Genet, 64, 600-607. 17. Cabot A, Rozet JM, Gerber S, Perrault I, Ducroq D, Smahi A, Souied E, & et al. (1999). A gene for X-linked idiopathic congenital nystagmus (NYS1) maps to chromosome Xp11.4-11.3. Am J Hum Genet, 64, 1141-1146. 18. Tarpey P, Thomas S, Sarvananthan N, Mallya U, Lisgo S, Talbot CJ, Roberts EO, & et al. (2006). Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus. Nat Genet, 38(11), 1242-1244. 19. Novel human pathological mutations. (2007). Hum Genet, 122, 413-420. 20. Thomas A, Proudlock FA, Sarvanantan N, Roberts EO, Awan M, McLean R, Surendran M, & et al. (2008). Phenotypical characteristics of idiopathic infantile nystagmus with and without mutations in FRMD7. Brain, 131, 1259-1267. 21. Self JE, Shawkat F, Malpas CT, Thomas S, Harris CM, Hodgkins PR, Chen X, & et al. (2007). Allelic variation of the FRMD7 gene in congenital idiopathic nystagmus. Arch Ophthalmol, 125(9), 1255-1263. 22. Zhang Q, Xiao X, Li S, Guo X. (2007). FRMD7 mutations in Chinese families with X-linked congenital motor nystagmus. Mol Vis, 13, 1375-1378. 23. Shiels A, Bennett TM, Prince JB, Tychsec L. (2007). X-linked idiopathic infantile nystagmus associated with a missense mutation in FRMD7. Mol Vis, 13, 2233-2241. 24. Zhang B, Liu Z, Zhao G, Xie X, Yin X, Hu Z, Xu S, & et al. (2007). Novel mutations of the FRMD7 gene in X-linked congenital motor nystagmus. Mol Vis, 13, 1674-1679. 25. He X, Gu F, Wang Y, Yan J, Zhang M, Huang S, Ma X. (2008). A novel mutation in FRMD7 causing X-linked idiopathic congenital nystagmus in a large family. Mol Vis, 14, 56-60. 26. Li N, Wang L, Cui L, Zhang L, Dai S, Li H, Chen X, & et al. (2008). Five novel mutations of FRMD7 gene in Chinese families with X-linked infantile nystagmus. Mol Vis, 14, 733-738. 27. Zhou P, Wang Z, Zhang J, Hu L, Kong X. (2008). Identification of a novel GPR143 deletion in a Chinese family with X-linked congenital nystagmus. Mol Vis, 14, 1015-1019. 28. Abadi RV, Bjerre A. (2002). Motor and sensory characteristics of infantile nystagmus. Br J Ophthalmol, 86, 1152-1160. 29. Pritchard DJ, Korf BR.（2006）。醫用遺傳學精義。（Medical genetics at a glance）（姚侑廷譯）台北縣：藝軒出版社。（原作2003年出版） 30. 張建裕、張建國編（民國95年）。醫學分子診斷學（頁18-22）。台北縣：藝軒出版社。 31. 王亦榮（民國85年）：眼球震顫及其在教育上的因應。國立台南師範學院特教簡訊，第十期。 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41661 | - |
| dc.description.abstract | 先天性眼球震顫（CN），具有多種的遺傳模式，包括體染色體顯性（AD）、體染色體隱性（AR）及伴X染色體（X-linked）都有被報導過。在臨床上CN的盛行率約是1/1000~1/1500，以伴X染色體CN最常見，而體染色體隱性CN最為罕見。2006年，Tarpey等人利用連鎖分析法鑑定出第一個眼球震顫基因（FRMD7），確認其為造成伴X染色體CN之主要原因。而體染色體顯性CN有關聯性的基因座包括：6p12（NYS2）、7p11（NYS3）、15q11及18q22.3-q23，至於體染色體隱性CN則是因為個案極罕見，而尚未有任何發現。儘管已經發現了第一個眼球震顫基因，但是目前對於眼球震顫的病理機制仍然不明瞭，也缺乏有效的治療方式。
本實驗之研究對象是一個近親通婚（consanguineous mating）的體染色體隱性CN家庭，家中子代有兩名CN患者。因為此型個案極罕見，並無相關資料可供參考，所以我們決定利用短序列重複片段（STR）標記，針對23對染色體來進行初步分析。選用的標記主要是目前實驗室已應用於親子鑑定、造血幹細胞移植後追蹤，另一部分則是自國家衛生研究院之台灣多變異性標竿資料庫篩選的STR標記。 結果可以區分成三個部份，（1）『排除』，包括：Chromosome 1、2、4、5、6、7、8、9、10、13、18、20、21、22、X。（2）『無法排除』，包括：Chromosome 3、11、14、15、16、17。（3）『可疑』，包括：Chromosome 12、19。接下來的研究目標一是針對已報導過的CN候選基因座6p12、7p11、15q11、18q22.3-q23及FRMD7進行連鎖分析，排除可能性。二是以核型圖（karyotype）進行染色體分析，確認是否有染色體異常。三是選取其它STR markers再次進行PCR-STR，依照可疑、無法排除、排除三個階段順序，而19q、3p、2p、5q也列為優先分析區域。如此循序漸進的將目標縮小，試圖找到候選基因座。受限於家族樣本數不多，或許不容易找到候選基因座，但任何進一步的研究結果對此症都是一份貢獻。 | zh_TW |
| dc.description.abstract | Congenital nystagmus (CN) is genetically heterogeneous. The inheritance model is mainly X-linked CN, but autosomal dominant and autosomal recessive forms have been described. Prevalence rates for CN of 1 in 1000 to 1 in 1500 have been reported. In November 2006 Tarpey et al. identified 22 nystagmus causing mutations in the FERM domain-containing 7 (FRMD7) gene. At least three distinct loci for autosomal dominant CN, include 6p12 (NYS2), 7p11 (NYS3) and 18q22.3-q23. However, Autosomal recessive CN is very rare and no loci have been identified. The pathophysiological mechanisms underlying nystagmus are poorly understood. Identification of FRMD7 gene has created a number of researches which are likely to provide valuable insights into the function and development of the oculomotor pathways.
In this study, thirty-one short tandem repeats (STR) markers in a consanguineous mating family with autosomal recessive CN were analyzed. The result is based on STR analysis, we can group chromosomes into three types, include reject, un-reject and question. Further studies are still required to identify the target genes. Furthermore linkage analysis of this family with previously implicated loci and other STR markers is essential. It is hoped that this study will stimulate further investigations in this field. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T00:26:32Z (GMT). No. of bitstreams: 1 ntu-98-P95448009-1.pdf: 3342263 bytes, checksum: 9d6d3b7e4a9453a63b405e8a761a20f3 (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 口試委員會審定書………………………………………………………i
誌謝………………………………………………………………………ii 中文摘要………………………………………………………………iii 英文摘要……………………………………………………………… iv 一、緒論…………………………………………………………………1 1.1先天性眼球震顫之簡介……………………………………………1 1.1.1病理機制……………………………………………………………1 1.2先天性眼球震顫之相關基因研究……………………………………2 1.2.1 Autosomal dominant CN…………………………………………2 1.2.2 Autosomal recessive CN………………………………………3 1.2.3 X-linked CN………………………………………………………3 1.3疾病基因之研究技巧………………………………………………4 1.3.1遺傳標記……………………………………………………………4 1.3.2連鎖分析（linkage analysis）…………………………………5 1.4 PCR-STR原理………………………………………………………6 1.5研究動機………………………………………………………………6 二、實驗材料與儀器……………………………………………………8 2.1實驗材料………………………………………………………………8 2.1.1 DNA檢體……………………………………………………………8 2.1.2引子對………………………………………………………………8 2.1.3 DNA萃取試劑………………………………………………………8 2.1.4聚合酶連鎖反應試劑………………………………………………9 2.1.5毛細管電泳自動分析儀試劑………………………………………9 2.2實驗儀器………………………………………………………………9 2.2.1 65℃水浴箱…………………………………………………………9 2.2.2離心機………………………………………………………………9 2.2.3分光光譜儀…………………………………………………………9 2.2.4 PCR熱循環器………………………………………………………9 2.2.5毛細管電泳自動分析儀……………………………………………9 三、實驗方法……………………………………………………………10 3.1 萃取檢體之DNA……………………………………………………10 3.2 STR之選取…………………………………………………………10 3.3聚合酶鏈鎖反應（Polymerase Chain Reaction, PCR）……………10 3.4毛細管電泳自動化分析……………………………………………11 四、實驗結果…………………………………………………………12 4.1各STR之基因型……………………………………………………12 4.1.1 Chromosome 1……………………………………………………12 4.1.2 Chromosome 2……………………………………………………12 4.1.3 Chromosome 3……………………………………………………12 4.1.4 Chromosome 4……………………………………………………12 4.1.5 Chromosome 5……………………………………………………13 4.1.6 Chromosome 6……………………………………………………13 4.1.7 Chromosome 7……………………………………………………13 4.1.8 Chromosome 8……………………………………………………13 4.1.9 Chromosome 9……………………………………………………13 4.1.10 Chromosome 10…………………………………………………13 4.1.11 Chromosome 11…………………………………………………14 4.1.12 Chromosome 12…………………………………………………14 4.1.13 Chromosome 13…………………………………………………14 4.1.14 Chromosome 14…………………………………………………14 4.1.15 Chromosome 15…………………………………………………14 4.1.16 Chromosome 16…………………………………………………14 4.1.17 Chromosome 17…………………………………………………15 4.1.18 Chromosome 18…………………………………………………15 4.1.19 Chromosome 19…………………………………………………15 4.1.20 Chromosome 20…………………………………………………15 4.1.21 Chromosome 21…………………………………………………15 4.1.22 Chromosome 22…………………………………………………16 4.1.23 Chromosome X…………………………………………………16 五、討論………………………………………………………………17 六、參考文獻…………………………………………………………22 圖目錄 圖一、個案家庭之家族譜……………………………………………………………...25 圖二、個案家族之STR marker D1S1600之結果…………………………………….26 圖三、個案家族之STR markers D3S1358、TH01、D13S317、D16S539、D2S1338之結果………………………………………………………………………….27 圖四、個案家族之STR markers D19S433、vWA、TPOX、D18S51之結果………28 圖五、個案家族之STR markers XY、D5S818、FGA之結果………………………29 圖六、個案家族之STR markers D8S1179、D21S11、D7S820、CSF1PO之結果…30 圖七、個案家族之STR marker D6S475之結果………………………………………31 圖八、個案家族之STR markers Penta C、Penta E、Penta B之結果……………….32 圖九、個案家族之STR marker D9S301之結果……………………………………...33 圖十、個案家族之STR marker D10S2327之結果……………………………………34 圖十一、個案家族之STR marker D14S617之結果………………………………….35 圖十二、個案家族之STR marker D17S2196之結果…………………………………36 圖十三、個案家族之STR marker D19S254之結果………………………………….37 圖十四、個案家族之STR marker D20S470之結果………………………………….38 圖十五、個案家族之STR marker Penta D之結果……………………………………39 圖十六、個案家族之STR marker D22S683之結果………………………………….40 圖十七、個案家族之STR marker DXS101之結果……………………………………41 圖十八、個案家族之STR marker DXS424之結果…………………………………..42 圖十九、個案家族之STR marker DXS8377之結果…………………………………43 表目錄 表一、利用病史、理學檢查及眼球的運動記錄將眼球震顫予以分型……………….44 表二、先天性眼球震顫之相關基因…………………………………………………...45 表三、本實驗所使用的STR markers之位置…………………………………………46 表四、親子鑑定實驗室STR markers，PCR理想之試劑反應條件…………………..47 表五、多變異性標竿資料庫STR markers， PCR理想之試劑反應條件……………48 表六、個案家族之STR markers基因型………………………………………………49 表七、依STR markers分析結果將染色體分群……………………………………….51 表八、Affected之STR基因型為同合子型……………………………………………52 | |
| dc.language.iso | zh-TW | |
| dc.subject | 核型圖 | zh_TW |
| dc.subject | 候選基因座 | zh_TW |
| dc.subject | 先天性眼球震顫 | zh_TW |
| dc.subject | 近親通婚 | zh_TW |
| dc.subject | 短序列重複片段 | zh_TW |
| dc.subject | candidate genes | en |
| dc.subject | Congenital nystagmus (CN) | en |
| dc.subject | FERM domain-containing 7 (FRMD7) | en |
| dc.subject | short tandem repeats (STR) | en |
| dc.subject | consanguineous mating | en |
| dc.title | 體染色體隱性遺傳之先天性眼球震顫個案家庭之遺傳分析 | zh_TW |
| dc.title | Genetic Analysis of a Family with Autosomal Recessive Congenital Nystagmus | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 余家利,楊偉勛 | |
| dc.subject.keyword | 先天性眼球震顫,近親通婚,短序列重複片段,核型圖,候選基因座, | zh_TW |
| dc.subject.keyword | Congenital nystagmus (CN),FERM domain-containing 7 (FRMD7),short tandem repeats (STR),consanguineous mating,candidate genes, | en |
| dc.relation.page | 52 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-01-22 | |
| 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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