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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蘇怡寧 | |
dc.contributor.author | Yi-Ling Chen | en |
dc.contributor.author | 陳怡伶 | zh_TW |
dc.date.accessioned | 2021-06-15T05:08:15Z | - |
dc.date.available | 2010-09-09 | |
dc.date.copyright | 2010-09-09 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-07-26 | |
dc.identifier.citation | 1 Silver HK, Kiyasu W, George J, Deamer WC. Syndrome of congenital hemihypertrophy, shortness of stature, and elevated urinary gonadotrophins. Pediatrics 1953;12:368-75.
2 Russell A. A syndrome of intra-uterine dwarfism recognizable at birth with cranio-facial dysostosis, disproportionately short arms and other anomalies. Proc R Soc Med 1954;47:1040-4. 3. Price SM, Stanhope R, Garrett C, Preece MA, Trembath RC The spectrum of Silver-Russell syndrome: a clinical and molecular genetic study and new diagnostic criteria. J Med Genet 1999;36:837–842 4. Escobar V, Gleiser S, Weaver DD 1978 Phenotypic and genetic analysis of the Silver-Russell syndrome. Clin Genet 1978;13:278–288 5. Anderson J, Viskochil D, O’Gorman M, Gonzales C Gastrointestinal complications of Russell-Silver syndrome: a pilot study. Am J Med Genet 2002;113:15–19 6. Lai KYC, Skuse D, Stanhope R, Hindmarsh P. Cognitive abilities associated with the Silver-Russell syndrome. Arch Dis Child 1994;71:490-6. 7. Wetterau LA, Prakash-Cheng A. eMedicine.com, Silver-Russell Syndrome. 8.Wollman HA, Kirchner T, Enders H, Preece MA, Ranke MB: Growth and symptoms in Silver-Russell syndrome: Review on the basis 386 patients. Eur J Pediatr 1995;154:958–968. 9. Davies PSW, Valley R, Preece MA: Adolescent growth and pubertal progression in the Silver-Russell syndrome. Arch Dis Child 1988;63:130–135. 10 Albanese A, Stanhope R. GH treatment induces sustained catch-up growth in children with intrauterine growth retardation. Hormone Res 1997;48:173-7. 11.Stanhope R, Albanese A, Azcona C. Growth hormone treatment of Russell-Silver syndrome. Hormone Res 1998;49(suppl 2):37-40. 12. Azcona C, Albanese A, Bareille P, Stanhope R. Growth hormone treatment in growth hormone-sufficient and-insufficient children with intrauterine growth retardation/Russell-Silver syndrome. Hormone Res 1998;50:22-7. 13. Ranke MB, Lindberg A.Height at Start, First-Year Growth Response and Cause of Shortness at Birth Are Major Determinants of adult height outcomes of short children born small for gestational age and Silver-Russell Syndrome treated with growth hormone: analysis of data from KIGS. Horm Res Paediatr. 2010; Apr 30. [Epub ahead of print] 14. Russell-Silver Syndrome. Saal HM. [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.2002 Nov 2 [updated 2007 Mar 9]. 15. Abu-Amero S, Monk D, Frost J, Preece M, Stanier P, Moore G. The genetic aetiology of Silver-Russell syndrome. J Med Genet 2008;45:193–9. 16. Hitchins MP, Stanier P, Preece MA, Moore GE. Silver-Russell syndrome: a dissection of the genetic aetiology and candidate chromosomal regions. J Med Genet 2001;38:810–9. 17. Lahiri A, Lester R. Hand anomalies in Russell Silver syndrome. J Plast Reconstr Aesthet Surg. 2009;62:462-5. 18. Ire`ne Netchine, Sylvie Rossignol, Marie-Noe¨lle Dufourg, Salah Azzi, et al ,11p15 Imprinting center region 1 loss of methylation is a common and specific cause of typical Russell-Silver Syndrome: clinical scoring system and epigenetic-phenotypic correlations. J Clin Endocrinol Metab 2007;92:3148–3154. 19. Sempe´ M, Pedron G, Roy-Penot M Auxologie, me´thode et se´quences. Paris: Theraplix 1979 20. Usher R, McLean F 1969 Intrauterine growth of live-born Caucasian infants at sea level: standards obtained from measurements in 7 dimensions of infants born between 25 and 44 weeks of gestation. J Pediatr 1969 ;74:901–910 21. Bartholdi D, Krajewska-Walasek M, Ounap K, Gaspar H, Chrzanowska KH, Ilyana H, Kayserili H, Lurie IW, Schinzel A, Baumer A. Epigenetic mutations of the imprinted IGF2-H19 domain in Silver-Russell syndrome (SRS): results from a large cohort of patients with SRS and SRS-like phenotypes. J Med Genet. 2009;46:192-7. 22. Reik W, Walter J Genomic imprinting: parental influence on the genome. Nat Rev Genet 2001; 2:21–32 23. Monk, D. et al. Chromosome 7p disruptions in Silver Russell syndrome: delineating an imprinted candidate gene region. Hum. Genet. 2002;111:376–387 24. Leach, N.T. et al. Maternally inherited duplication of chromosome 7, dup(7)(p11.2p12), associated with mild cognitive deficit without features of Silver-Russell syndrome. Am. J. Med. Genet A. 2007;143:1489–1493 25. Kotzot, D. et al. (1995) Uniparental disomy 7 in Silver-Russellsyndrome and primordial growth retardation. Hum. Mol. Genet. 1995;4:583–587 26. Webb T, Clarke D, Hardy CA, Kilpatrick MW, Corbett J, Dahlitz M: A clinical, cytogenetic, and molecular study of 40 adults with the Prader- Willi syndrome. J Med Genet 1995;32:181–185. 27. Malcolm S, Clayton-Smith J, Nichols M, et al: Uniparental disomy in Angelman’s syndrome. Lancet 1991;337:694–697. 28. Ramesar R, Babayar M, Viljoen D: Molecular investigation of familial Beckwith-Wiedemann syndrome: a model for paternal imprinting. Eur J Hum Genet 1993;1:109–113. 29. Hall JG. Unilateral disomy as a possible explanation for Russell-Silver syndrome. J Med Genet 1990;27:141-2. 30 Voss D, Ben-Simon E, Avital A, et al: Isodisomy of chromosome 7 in a patient with cystic fibrosis: Could uniparental disomy be common in humans? Am J Hum Genet 1989;45:373– 380. 31 Spence JE, Persiaccante RG, Greig GM, et al: Uniparental disomy as a mechanism for human genetic disease. Am J Hum Genet 1995;42:217–226. 32.Preece MA, Price SM, Davies V, Clough L, Stanier P, Trembath RC, Moore GE. Maternal uniparental disomy 7 in Silver-Russell syndrome. J Med Genet 1997;34:6–9. 33. Eggermann T, Eggermann K, Schönherr N. Growth retardation versus overgrowth: Silver-Russell syndrome is genetically opposite to Beckwith-Wiedemann syndrome. Trends Genet.2008;24:195-204 34.Charalambous, M. et al. Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism. Proc. Natl. Acad. Sci. U. S. A. 2003;100: 8292–8297 35.Wang, L. et al. Peripheral disruption of the Grb10 gene enhances insulin signaling and sensitivity in vivo. Mol. Cell. Biol. 2007;27: 6497–6505 36. Shiura, H. et al. Meg1/Grb10 overexpression causes postnatal growth retardation and insulin resistance via negative modulation of the IGF1R and IR cascades. Biochem. Biophys. Res. Commun. 2005;329:909–916 37. Hannula, K. et al. A narrow segment of maternal uniparental disomy of chromosome 7q31-qter in Silver-Russell syndrome delimits a candidate gene region. Am. J. Hum. Genet. 2001;68:247–253 38. Reboul, M-P. et al. (2006) Mosaic maternal uniparental isodisomy for chromosome 7q21-qter. Clin. Genet. 2006;70:207–213 39. Eggermann, T. et al. Is maternal duplication of 11p15 associated with Silver-Russell syndrome? J. Med. Genet. 2005;42:e26 40.Netchine, I. et al. 11p15 ICR1 loss of methylation is a commonand specific cause of typical Russell-Silver syndrome: clinical scoring system and epigenetic-phenotypic correlations. J. Clin. Endocrinol. Metab. 2007;92:3148–3154 41.Gicquel, C. et al. Epimutation of the telomeric imprinting centerregion on chromosome 11p15 in Silver Russell syndrome. Nat. Genet.2005;37:1003–1007 42.Bliek, J. et al. Hypomethylation of the H19 gene causes not only Silver-Russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype. Am. J. Hum. Genet.2006;78: 604–614 43.Eggermann, T. et al. Use of multiplex ligation-dependent probe amplification increases the detection rate for 11p15 epigenetic alterations in Silver-Russell syndrome. Clin. Genet. 2008;73:79–84 44. Horike S-I, Ferreira JCP, Meguro-Horike M, Choufani S, Smith AC, Shuman C, Meschino W, Chitayat D, Zackai E, Scherer SW, Weksberg R. Screening of DNA methylation at the H19 promoter or the distal region of its ICR1 ensures efficient detection of chromosome 11p15 epimutations in Russell–Silver syndrome. Am J Med Genet Part A 2009;149A:2415–2423. 45. Azzi S, Rossignol S, Steunou V, Sas T, Thibaud N, Danton F, Le Jule M, Heinrichs C, Cabrol S, Gicquel C, Le Bouc Y, Netchine I.Multilocus methylation analysis in a large cohort of 11p15-related foetal growth disorders (Russell Silver and Beckwith Wiedemann syndromes) reveals simultaneous loss of methylation at paternal and maternal imprinted loci. Hum. Mol. Genet. 2009;184:4724-33 46. Weksberg R, Smith AC, Squire J, Sadowski P. Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal development. Hum Mol Genet 2003;12:R61–R68. 47. Schonherr N, Meyer E, Roos A, Schmidt A, Wollmann HA, Eggermann T. The centromeric 11p15 imprinting centre is also involved in Silver-Russell syndrome. J Med Genet 2007;44:59–63. 48. M.W. Moore, L.G. Dietz, B. Tirtorahardjo, P.D. Cotter, A multiplex methylation PCR assay for identification of uniparental disomy of chromosome 7, Hum. Mutat. 2003;21:645-648. 49. Kagami M, Nagai T, Fukami M, Yamazawa K, Ogata T. Silver-Russell syndrome in a girl born after in vitro fertilization: partial hypermethylation at the differentially methylated region of PEG1/. MEST J Assist Reprod Genet 2007;24:131-136. 50. Marques CJ, Costa P, Vaz B, Carvalho F, Fernandes S, Barros A, Sousa M. Abnormal methylation of imprinted genes in human sperm is associated with oligozoospermia. Mol Hum Reprod 2008;14:67-74. 51. Scho¨herr N, Ja¨ger S, Ranke MB, Wollmann HA, Binder G, Eggermann T. No evidence for isolated imprinting mutations in the PEG1/MEST locus in Silver-Russell patients. Eur J Med Genet 2008;51:322-324. 52. Largo RH, Wa¨lli R, Duc G, Fanconi A, Prader A. Evaluation of perinatal growth. Presentation of combined intra- and extrauterine growth standards for weight, length and head circumference. Helv Paediatr Acta 1980;35:419–36. 53. Prader A, Largo RH, Molinari L, Issler C. Physical growth of Swiss children from birth to 20 years of age. First Zurich longitudinal study of growth and development. HelvPaediatr Acta Suppl 1989;52:1–125. 54. Nationwide singleton birth weight percentiles by gestational age in Taiwan, 1998-2002.Hsieh WS, Wu HC, Jeng SF, Liao HF, Su YN, Lin SJ, Hsieh CJ, Chen PC. Acta Paediatr Taiwan.2006;47:25-33. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46422 | - |
dc.description.abstract | 目的: 羅素-西弗氏症是一罕見的先天疾病,其臨床表現極為多樣亦具有多種分子變異曾在文獻中被提及。羅素-西弗氏症的臨床表現特色為子宮內生長遲滯、身材矮小及典型的臉部特徵等。目前關於羅素-西弗氏症診斷標準尚無定論,第七對染色體母源單親二體症(maternal uniparental disomy of chromosome 7)及第十一對染色體短臂印記中心甲基化低下(hypomethylation of the imprinting in 11p15)是目前羅素-西弗氏症最常被提及的分子變異類型。但台灣目前尚無關於羅素-西弗氏症個案之分子診斷與臨床分析的相關研究。
方法: 我們收集由臨床醫師診斷為羅素-西弗氏症個案轉介至本研究中心之個案,針對第七對染色體母源單親二體症(maternal uniparental disomy of chromosome 7)及第十一對染色體短臂印記中心甲基化異常進行分析,並回溯收集其臨床表現以進行分子診斷與表現型相關分析。此研究中,我們設計一個羅素-西弗氏症臨床表現評分表來量化個案之表現型。 結果: 在我們研究發現第七對染色體母源單親二體症及第十一對染色體短臂印記中心甲基化低下分別在羅素-西弗氏症個案占了3.6%和 26.8%的比例。這些具有突變之個案其臨床表現以羅素-西弗氏症臨床表現評分表評估均大於或等於六分, 而此評分方式顯示: 相較於第十一對染色體短臂印記中心甲基化低下, 第七對染色體母源單親二體症的病患症狀均較輕微。在羅素-西弗氏症與疑似羅素-西弗氏症兩組個案中,子宮內生長遲緩、出生後生長遲緩、典型臉部特徵、頭部/軀幹或肢體不對稱性與第五手指彎斜的比率,均有明顯差異。 結論: 在本研究中,針對具有羅素-西弗氏症表現型的個案,分析其分子診斷結果,有分子診斷異常佔30.4 % ,其中第七對染色體母源單親二體症及第十一對染色體短臂印記中心甲基化低下分別在羅素-西弗氏症個案占了3.6%和 26.8%的比例。運用我们提出的羅素-西弗氏症臨床表現評分表,我們可以針對疑似羅素-西弗氏症之個案臨床表現進行評分予以量化。在本研究中,羅素-西弗氏症臨床表現評分大於或等於六分是評估可否找到羅素-西弗氏症分子診斷異常的分岐點。 | zh_TW |
dc.description.abstract | Objective: Silver-Russell syndrome (SRS) is a clinical and genetically heterogenous disorder characterized by severe intrauterine growth restriction, postnatal growth retardation, and specific dysmorphisms. But no consensus on clinical diagnostic criteria was made. Maternal uniparental
disomy of chromosome 7 and hypomethylation of the imprinting in 11p15 are the major epigenetic disturbance in patients of Silver-Russell syndrome. The incidence of epigenetic disturbance in Taiwanese patients of Silver-Russell syndrome and the epigenetic-phenotype analysis have never been surveyed. Materials and methods: We report on our experience of molecular testing in 107 Taiwanese patients referred for routine diagnostics of Silver-Russell syndrome. We also retrospectively investigated the clinical manifestations of those probands with suspected Silver-Russell syndrome phenotypes. We designed a clinical SRS scoring system to help the pediatrians in clinical setting . Results: The molecular results in our study cohort showed that maternal uniparental disomy of chromosome 7 and hypomethylation of the H19 imprinted region in 11p15 accounts for the epigenetic disturbance in 3.6% and 26.8% of patients with clinically scored as SRS group (n=56). respectively. All cases with epimutation were scored >= 6 by the clinical SRS scoring system. Maternal uniparental disomy of chromosome 7 carriers showed relatively mild Silver-Russell syndrome phenotype as compared with 11p15 epimutation carrier. The percentage of small for gestational age, postnatal growth retardation, typical facies, aymmetry and clinodactyly of 5th fingers was significantly different between SRS group and SRS-like group. Conclusions:The detection rate of epigenetic anomalies in our study cohort of 56 Taiwanese individuals with SRS phenotypes was around 30.4 %; epimutations at the PEG1/MEST locus and the H19/IGF2 locus occurred in about 3.6% and 26.8% of patients with SRS respectively. By our new clinical SRS scoring system, we can quantify the phenotype severity, and it showed that “clinical SRS score 6” was a good discrimination point to distinguish the cases with or without epimutation for SRS inour study. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T05:08:15Z (GMT). No. of bitstreams: 1 ntu-99-P97448002-1.pdf: 1080222 bytes, checksum: 766d171141b9c90020c15a3b71b5d9ab (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………………………………………………………… iv 英文摘要………………………………………………………… v Chapter 1. Introduction …………………………………… 1 1.1 Introduction …………………………………………… 1 1.2 Literatures reviews ………………………………… 1 1.2.1The Clinical Manifestation and Management of Silver-Russell Syndrome …………………………………………… 1 1.2.2 Diagnostic Criteria for Silver-Russell Syndrome …… 4 1.2.3 The Genetic Etiology of Silver-Russell Syndrome …… 6 1.2.3.1 Imprinted Genes and Fetal Growth ………………… 7 1.2.3.2 Chromsome 7 and SRS …………………………………… 7 1.2.3.3 Imprinted 11p15 region ……………………………… 10 Chapter 2. Objectives ……………………………………… 12 Chapter 3. Material and Methods ………………………… 13 3.1 Study population & DNA extraction Study population ……………………………………………………………………… 13 3.2 Definition of Silver-Russell Syndrome ……………… 13 3.3 Definition of New SRS scoring system ……………… 14 3.4 Molecular evaluation ………………………………… 15 3.4.1 MLPA …………………………………………………… 15 3.4.2 MS-HRM ………………………………………………… 16 3.4.2.1 Sodium bisulfite treatment of DNA…………… 16 3.4.2.2 MS-HRM for H19 hypomethylation and maternal UPD7………………………………………………………………… 16 3.4.2.3 MS-HRM for KCNQ1OT1……………………………… 18 3.4.3 Methylation-specific multiplex PCR …………… 18 3.5 Statistical Analysis ……………………………… 19 Chapter 4. Results……………………………………… 20 4.1 Molecular evaluation in Taiwanese Patients with SRS or SRS-like Phenotypes …………………………………… 20 4.1.1 Maternal UPD7 ……………………………………… 20 4.1.2 H19 and KCNQ1OT1 ICR methylation………………… 20 4.2 Epigenetic-Phenotype Correlation in Taiwanese Patients with SRS or SRS-like Phenotypes ………………………… 21 4.2.1 SRS diagnostic criteria ………………………… 21 4.2.2 New Clinical SRS scoring system ………………… 22 Chapter 5. Discussion …………………………………… 24 Chapter 6. Conclusion …………………………………… 29 References ………………………………………………… 51 Figure 1 Members of the insulin-like growth factor system and their interactions as Silver-Russell syndrome (SRS) candidate genes ……………………………………… 30 Figure 2 Physical map of the imprinted gene cluster in the diagram of human chromosome 11p15.5……………………… 31 Figure 3 Representation of the 11p15 region and its imprinting related disorders …………………………… 32 Figure 4 Flowchart of epigenetic mutation workup and clinical phenotype evaluation for all 107 patients suspected of having Silver-Russell syndrome …………………………………………………………………… 33 Figure 5 Comparsion of the percentage distribution of clinical features in SRS and SRS-like groups ………………………………………………………………… 34 Figure 6 The scatter plot of GA(gestational age) versus BW(birth weight) in SRS and SRS-like groups (Female) ………………………………………………………………… 35 Figure 7 The scatter plot of GA(gestational age) versus BW(birth weight) in SRS and SRS-like groups (Male) …………………………………………………………………… 36 Figure 8 Comparion of clinical SRS score in four groups including H19 hypomethylation, maternal UPD7, idiopathic SRS and SRS-like phenotype …………………………… 37 Table 1 Characteristics of Silver-Russell syndromerl…… ……………………………………………………………………38 Table 2 Clinical features observed in patients with Silver-Russell syndrome …………………………………………… 39 Table 3 Clinical Silver-Russell syndrome Score ………………………………………………………………… 40 Table 4 Characteristics of study population…………… 42 Table 5 New Clinical Silver-Russell Syndrome (SRS) Score …………………………………………………………………… 43 Table 6 Frequency of methylation defects and mUPD7 in the patient cohort ………………………………………… 44 Table 7 Clinical Characteristics of SRS and SRS-like patients …………………………………………………… 45 Table 8 Clinical Characteristics of Patients with Silver-Russell Syndrome ……………………………………… 46 Table 9 Clinical features of maternal UPD(7)………… 47 Table 10 Clinical Characteristics of SRS and SRS-like patients(according to SRS scoring system) ……………………………………………………………… 48 Table 11 Distribution of clinical severity scores in different groups …………………………………………… 49 Table 12 Distribution of clinical scoring system in different groups …………………………………………… 50 | |
dc.language.iso | en | |
dc.title | 台灣羅素-西弗氏症及擬羅素-西弗氏症個案之分子診斷與臨床分析 | zh_TW |
dc.title | The Epigenetic-Phenotype Analysis in Taiwanese Patients with
Silver-Russell Syndrome (SRS) or SRS-like Phenotypes | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 楊偉勛,林炫沛 | |
dc.subject.keyword | 羅素-西弗氏症,羅素-西弗氏症臨床表現評分表,第十一對染色體短臂印記中心甲基化低下,第七對染色體母源單親二體症, | zh_TW |
dc.subject.keyword | Silver-Russell syndrome,clinical SRS scoring system,maternal uniparental disomy of chromosome 7,H19 hypomethylation,epigenetic-phenotype analysis, | en |
dc.relation.page | 58 | |
dc.rights.note | 有償授權 | |
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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