Please use this identifier to cite or link to this item:
標題: 利用染色體微陣列分析產前診斷的標記染色體
The use of chromosomal microarray analysis in prenatal diagnosis of small supernumerary marker chromosome
作者: 黃閔輝
Min-Hui Huang
關鍵字: 產前診斷;標記染色體;微陣列比較基因組雜交;Prenatal diagnosis;sSMC;array CGH
引用: 林芯妤. 'Update of First Trimester and Second Trimester Invasive Genetic Diagnosis.' prenatal screening tests and their related problems. 2015. 黃閔輝, 賴惠玲, 何素鵬. '流產與染色體異常.' 雙北檢驗醫學雜誌 3.2(2016): 4-8. 互動百科. 'Amniotic Fluid.' 2015. Web. 邱淑媞. '國民健康署年報.' Ed. 國民健康署2014. Shaffer, Lisa G, Jean McGowan-Jordan, and Michael Schmid. ISCN 2013:An International System for Human Cytogenetic Nomenclature (2013). Karger Medical and Scientific Publishers, 2013. Zneimer, S. Cytogenetic Abnormalities: Chromosomal, Fish, and Microarray-Based Clinical Reporting and Interpretation of Result. John Wiley & Sons, 2014. Abad, David Escribano, et al. 'Pallister-Killian Syndrome Presenting with a Complex Congenital Heart Defect and Increased Nuchal Translucency.' Journal of ultrasound in medicine 25.11 (2006): 1475-80. Alfi, O. S., G. N. Donnell, and A. Derencsenyi. 'C-Banding of Human Chromosomes Produced by D.N.Ase.' Lancet 2.7827 (1973): 505. Bartels, I., et al. 'Supernumerary Small Marker Chromosome (Smc) and Uniparental Disomy 22 in a Child with Confined Placental Mosaicism of Trisomy 22: Trisomy Rescue Due to Marker Chromosome Formation.' Cytogenet Genome Res 101.2 (2003): 103-5. Bartsch, O., et al. 'Forty-Two Supernumerary Marker Chromosomes (Smcs) in 43,273 Prenatal Samples: Chromosomal Distribution, Clinical Findings, and Upd Studies.' Eur J Hum Genet 13.11 (2005): 1192-204. Battaglia, A. 'The Inv Dup (15) or Idic (15) Syndrome (Tetrasomy 15q).' Orphanet J Rare Dis 3 (2008): 30. Benn, P. A., and L. Y. Hsu. 'Incidence and Significance of Supernumerary Marker Chromosomes in Prenatal Diagnosis.' Am J Hum Genet 36.5 (1984): 1092-102. . Bielanska, M. M., M. M. Khalifa, and A. M. Duncan. 'Pallister-Killian Syndrome: A Mild Case Diagnosed by Fluorescence in Situ Hybridization. Review of the Literature and Expansion of the Phenotype.' Am J Med Genet 65.2 (1996): 104-8. Brondum-Nielsen, K., and M. Mikkelsen. 'A 10-Year Survey, 1980-1990, of Prenatally Diagnosed Small Supernumerary Marker Chromosomes, Identified by Fish Analysis. Outcome and Follow-up of 14 Cases Diagnosed in a Series of 12,699 Prenatal Samples.' Prenat Diagn 15.7 (1995): 615-9. Caspersson, T., et al. 'Chemical Differentiation Along Metaphase Chromosomes.' Experimental Cell Research 49.1 (1968): 219-22. Caspersson, T., et al. 'Identification of Human Chromosomes by DNA-Binding Fluorescent Agents.' Chromosoma 30.2 (1970): 215-27. Cereda, A., and J. C. Carey. 'The Trisomy 18 Syndrome.' Orphanet J Rare Dis 7 (2012): 81. Chang, Y. W., et al. 'An Overview of a 30-Year Experience with Amniocentesis in a Single Tertiary Medical Center in Taiwan.' Taiwan J Obstet Gynecol 51.2 (2012): 206-11. Chen, C. P. 'Chromosomal Abnormalities Associated with Omphalocele.' Taiwan J Obstet Gynecol 46.1 (2007): 1-8. Chen, C. P., et al. 'Abnormally Flat Facial Profile on Two- and Three-Dimensional Ultrasound and Array Comparative Genomic Hybridization for the Diagnosis of Pallister-Killian Syndrome.' Taiwan J Obstet Gynecol 49.1 (2010): 124-8. Chen, Chih-Ping, and Shu-Chin Chien. 'Prenatal Sonographic Features of Pallister-Killian Syndrome.' Journal of Medical Ultrasound 18.2 (2010): 43-53. Choo, KH Andy. 'Centromere DNA Dynamics: Latent Centromeres and Neocentromere Formation.' The American Journal of Human Genetics 61.6 (1997): 1225-33. Choudhary, M. G., et al. 'Derivative 11;22 (Emanuel) Syndrome: A Case Report and a Review.' Case Rep Pediatr 2013 (2013): 237935. Crocker, J., and P. Nar. 'Nucleolar Organizer Regions in Lymphomas.' J Pathol 151.2 (1987): 111-8. Crolla, J. A., et al. 'Supernumerary Marker 15 Chromosomes: A Clinical, Molecular and Fish Approach to Diagnosis and Prognosis.' Hum Genet 95.2 (1995): 161-70. Crolla, J. A., et al. 'Fish and Molecular Study of Autosomal Supernumerary Marker Chromosomes Excluding Those Derived from Chromosomes 15 and 22: I. Results of 26 New Cases.' American Journal of Medical Genetics 75.4 (1998): 355-66. Daniel, A., and P. Malafiej. 'A Series of Supernumerary Small Ring Marker Autosomes Identified by Fish with Chromosome Probe Arrays and Literature Review Excluding Chromosome 15.' Am J Med Genet A 117A.3 (2003): 212-22. de Ravel, Thomy JL, et al. 'Post‐Zygotic Origin of Isochromosome 12p.' Prenatal diagnosis 24.12 (2004): 984-88. Dunn, P. M. 'Dr Langdon Down (1828-1896) and 'Mongolism'.' Archives of Disease in Childhood 66.7 Spec No (1991): 827-28. Edwards, J. H., et al. 'A New Trisomic Syndrome.' Lancet 1.7128 (1960): 787-90. Ellis, JR, Ruth Marshall, and LS Penrose. 'An Aberrant Small Acrocentric Chromosome.' Annals of human genetics 26.1 (1962): 77-83. Print. Emanuel, B. S., E. H. Zackai, and L. Medne. 'Emanuel Syndrome.' Genereviews(R). Eds. Pagon, R. A., et al. Seattle (WA)1993. Ford, C. E., et al. 'A Sex-Chromosome Anomaly in a Case of Gonadal Dysgenesis (Turner's Syndrome).' The Lancet 273.7075 (1959): 711-13. Froland, A., G. Holst, and E. Terslev. 'Multiple Anomalies Associated with an Extra Small Autosome.' Cytogenetics 2 (1963): 99-106. Fuchs, F., and P. Riis. 'Antenatal Sex Determination.' Nature 177.4503 (1956): 330. Gartler, Stanley M. 'The Chromosome Number in Humans: A Brief History.' Nature Review| Genetics 7 (2006): 655. Genevieve, D, et al. 'Mild Phenotype in a 15‐Year‐Old Boy with Pallister–Killian Syndrome.' American Journal of Medical Genetics Part A 116.1 (2003): 90-93. Gilgenkrantz, S., et al. 'Mosaic Tetrasomy 12p.' Clin Genet 28.6 (1985): 495-502. Gillberg, C., et al. 'Autism Associated with Marker Chromosome.' J Am Acad Child Adolesc Psychiatry 30.3 (1991): 489-94. Glass, B. 'Theophilus Shickel Painter: August 22, 1889-October 5, 1969.' Biogr Mem Natl Acad Sci 59 (1990): 309-37. Goodpasture, C., and S. E. Bloom. 'Visualization of Nucleolar Organizer Regions Im Mammalian Chromosomes Using Silver Staining.' Chromosoma 53.1 (1975): 37-50. Graf, M. D., et al. 'Redefining the Risks of Prenatally Ascertained Supernumerary Marker Chromosomes: A Collaborative Study.' J Med Genet 43.8 (2006): 660-4. Gruchy, N., et al. 'Pregnancy Outcomes in 188 French Cases of Prenatally Diagnosed Klinefelter Syndrome.' Hum Reprod 26.9 (2011): 2570-5. Hodge, J. C., et al. 'Array Cgh on Unstimulated Blood Does Not Detect All Cases of Pallister-Killian Syndrome: A Skin Biopsy Should Remain the Diagnostic Gold Standard.' Am J Med Genet A 158A.3 (2012): 669-73. Hodge, Jennelle C, et al. 'Array Cgh on Unstimulated Blood Does Not Detect All Cases of Pallister–Killian Syndrome: A Skin Biopsy Should Remain the Diagnostic Gold Standard.' Am J Med Genet A 158.3 (2012): 669-73. Hook, E. B., and P. K. Cross. 'Extra Structurally Abnormal Chromosomes (Esac) Detected at Amniocentesis: Frequency in Approximately 75,000 Prenatal Cytogenetic Diagnoses and Associations with Maternal and Paternal Age.' Am J Hum Genet 40.2 (1987): 83-101. Hook, Ernest B. 'Rates of Chromosome Abnormalities at Different Maternal Ages.' Obstetrics & Gynecology 58.3 (1981): 282-85. Hsiao, Chien-Chou, et al. 'Changing Clinical Presentations and Survival Pattern in Trisomy 18.' Pediatrics & Neonatology 50.4 (2009): 147-51. Huang, B., et al. 'Refined Molecular Characterization of the Breakpoints in Small Inv Dup(15) Chromosomes.' Hum Genet 99.1 (1997): 11-7. Huang, B., et al. 'Supernumerary Marker Chromosomes Detected in 100,000 Prenatal Diagnoses: Molecular Cytogenetic Studies and Clinical Significance.' Prenat Diagn 26.12 (2006): 1142-50. Ilbery, PL, CW Lee, and SM Winn. 'Incomplete Trisomy in a Mongoloid Child Exhibiting Minimal Stigmata.' The Medical journal of Australia 48 (1961): 182. Jafari-Ghahfarokhi, H., et al. 'Small Supernumerary Marker Chromosomes and Their Correlation with Specific Syndromes.' Adv Biomed Res 4 (2015): 140. Jancevska, S., et al. 'Emanuel Syndrome (Es): New Case-Report and Review of the Literature.' Prilozi 36.1 (2015): 205-8. Jedraszak, G., et al. 'Severe Psychomotor Delay in a Severe Presentation of Cat-Eye Syndrome.' Case Rep Genet 2015 (2015): 943905. Kotzot, D., et al. 'Isochromosome 18p Results from Maternal Meiosis Ii Nondisjunction.' Eur J Hum Genet 4.3 (1996): 168-74. Leube, Barbara, et al. 'Clinical, Cytogenetic, and Molecular Observations in a Patient with Pallister‐Killian‐Syndrome with an Unusual Karyotype.' American Journal of Medical Genetics Part A 123.3 (2003): 296-300. Liehr, T, U Claussen, and H Starke. 'Small Supernumerary Marker Chromosomes (Ssmc) in Humans.' Cytogenetic and genome research 107.1-2 (2004): 55-67. Liehr, T., et al. 'Somatic Mosaicism in Cases with Small Supernumerary Marker Chromosomes.' Curr Genomics 11.6 (2010): 432-9. Liehr, Thomas 'Familial Small Supernumerary Marker Chromosomes Are Predominantly Inherited Via the Maternal Line.' Genetics IN Medicine 8 (2006): 459-62. Liehr, Thomas, and Anja Weise. 'Frequency of Small Supernumerary Marker Chromosomes in Prenatal, Newborn, Developmentally Retarded and Infertility Diagnostics.' International journal of molecular medicine 19.5 (2007): 719-32. McTaggart, K. E., et al. 'Cat Eye Syndrome Chromosome Breakpoint Clustering: Identification of Two Intervals Also Associated with 22q11 Deletion Syndrome Breakpoints.' Cytogenet Cell Genet 81.3-4 (1998): 222-8. Moorhead, P. S., et al. 'Chromosome Preparations of Leukocytes Cultured from Human Peripheral Blood.' Experimental Cell Research 20.3 (1960): 613-16. Nicolaides, K. H. 'Screening for Fetal Aneuploidies at 11 to 13 Weeks.' Prenat Diagn 31.1 (2011): 7-15. Pallister, P. D., et al. 'The Pallister Mosaic Syndrome.' Birth Defects Orig Artic Ser 13.3B (1977): 103-10. Paoloni‐Giacobino, A, MA Morris, and SP Dahoun. 'Prenatal Supernumeray R (16) Chromosome Characterized by Multiprobe Fish with Normal Pregnancy Outcome.' Prenatal diagnosis 18.7 (1998): 751-52. Patau, K., et al. 'Multiple Congenital Anomaly Caused by an Extra Autosome.' Lancet 1.7128 (1960): 790-3. Pinkel, Dr, T Straume, and JW Gray. 'Cytogenetic Analysis Using Quantitative, High-Sensitivity, Fluorescence Hybridization.' Proceedings of the National Academy of Sciences 83.9 (1986): 2934-38. Plaiasu, Vasilica, et al. 'A Rare Chromosomal Disorder-Isochromosome 18p Syndrome.' Romanian Journal of Medical Practice 6.2 (2011). Polityko, A. D., et al. 'Pallister-Killian Syndrome: Rapid Decrease of Isochromosome 12p Frequency During Amniocyte Subculturing. Conclusion for Strategy of Prenatal Cytogenetic Diagnostics.' J Histochem Cytochem 53.3 (2005): 361-4. Reynolds, J. F., et al. 'Isochromosome 12p Mosaicism (Pallister Mosaic Aneuploidy or Pallister-Killian Syndrome): Report of 11 Cases.' Am J Med Genet 27.2 (1987): 257-74. Robinson, Wendy P, et al. 'Uniparental Disomy Explains the Occurrence of the Angelman or Prader-Willi Syndrome in Patients with an Additional Small Inv Dup (15) Chromosome.' Journal of medical genetics 30.9 (1993): 756-60. Sachs, E. S., et al. 'Marker Chromosomes in a Series of 10,000 Prenatal Diagnoses. Cytogenetic and Follow-up Studies.' Prenat Diagn 7.2 (1987): 81-9. Schachenmann, G., et al. 'Chromosomes in Coloboma and Anal Atresia.' Lancet 2.7406 (1965): 290. Schena, Mark, et al. 'Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray.' Science 270.5235 (1995): 467. Print. Schrock, EDMS, et al. 'Multicolor Spectral Karotyping of Human Chromosomes.' Science 273.5274 (1996): 494. Schulze, A., and J. Downward. 'Navigating Gene Expression Using Microarrays--a Technology Review.' Nat Cell Biol 3.8 (2001): E190-5. Seabright, M. 'A Rapid Banding Technique for Human Chromosomes.' Lancet 2 (1971): 971-72. Simpson, J. L. 'Causes of Fetal Wastage.' Clin Obstet Gynecol 50.1 (2007): 10-30. Steele, MarkW, and W. Roy Breg. 'Chromosome Analysis of Human Amniotic-Fluid Cells.' The Lancet 287.7434 (1966): 383-85. Tjio, Joe Hin, and Albert Levan. 'The Chromosome Number of Man.' Hereditas 42.1-2 (1956): 1-6. Tseng, J. J., et al. 'Prenatal Diagnosis of Extrastructurally Abnormal Chromosomes: Clinical Experience and Literature Review.' J Chin Med Assoc 72.1 (2009): 29-33. Turner, Henry H. 'A Syndrome of Infantilism, Congenital Webbed Neck, and Cubitus Valgus.' Endocrinology 23.5 (1938): 566-74. Visootsak, J., and J. M. Graham, Jr. 'Klinefelter Syndrome and Other Sex Chromosomal Aneuploidies.' Orphanet J Rare Dis 1 (2006): 42. Wald, N. J., and H. S. Cuckle. 'Recent Advances in Screening for Neural Tube Defects and Down's Syndrome.' Baillieres Clin Obstet Gynaecol 1.3 (1987): 649-76. Wald, N. J., et al. 'Maternal Serum Screening for Down's Syndrome in Early Pregnancy.' BMJ 297.6653 (1988): 883-7. Wang, B. T., et al. 'Abnormalities in Spontaneous Abortions Detected by G-Banding and Chromosomal Microarray Analysis (Cma) at a National Reference Laboratory.' Mol Cytogenet 7 (2014): 33. Watson, E. J., and R. R. Gordon. 'A Case of Partial Trisomy 15.' J Med Genet 11.4 (1974): 400-2. Xiao, H., et al. 'Karyotype Analysis with Amniotic Fluid in 12365 Pregnant Women with Indications for Genetic Amniocentesis and Strategies of Prenatal Diagnosis.' J Obstet Gynaecol 36.3 (2016): 293-6. Zhao, W. W., et al. 'Robertsonian Translocations: An Overview of 872 Robertsonian Translocations Identified in a Diagnostic Laboratory in China.' PLoS One 10.5 (2015): e0122647. Best,PhD, Robert G, and Luis O Rohena,MD. 'Patau Syndrome_Background, Pathophysiology, Epidemiology.' 2015. Web. Leshin, Len. 'Trisomy 21: The Story of Down Syndrome.' 2009. Web. Woo, Joseph. 'A Short History of Amniocentesis, Fetoscopy and Chorionic Villus Sampling.' 2008. Web.
染色體微陣列比較基因體雜交(aCGH)是利用兩組基因體(對照組與檢測組),它們分別以不同的螢光標定後,再置於表面固著中期(metaphase)染色體的載玻片上進行競爭式雜交,然後標記測試DNA的螢光信號強度相對於參考DNA的螢光信號強度,可以顯現每個染色體上線性的表徵,從而鑑定拷貝數變化。本研究收集自2004年1月起至2015年12月止,共12年間羊膜穿刺染色體分析個案共68,087件,染色體異常率為2.17%,其中有59件為標記染色體,占總個案數的比率為0.087%,取其中45件個案羊水細胞進行染色體微陣列分析。發現了7個案例具有致病性基因的增益(gain),異常率佔16%(7/45),包括3例貓眼症候群的個案、1例Pallister-Killian syndrome個案、1例標記染色體15症候群個案。另2例微型標記染色體分別衍生自第11號染色體長臂和第12號染色體短臂。但是,案例8(細胞鑲嵌比率18.03%)經aCGH並未判定具有致病性基因增益,然而,以螢光原位雜交染色,檢出其異常標記染色體來自iso(18p),可能為一偽陰性案例。
傳統上,針對標記染色體(sSMC)檢測和特徵的描述,細胞遺傳學分析是一個金標(gold standard)技術,然而,本研究透過染色體微陣列比較基因組雜交技術分析,於分析的45個案例中,檢測出其中7個案例具有致病性基因增益,此結果顯示染色體微陣列分析確實可以提供遺傳諮詢更詳細的資訊,並對於未檢出具有致性基因增益的新生異常(de novo)個案,提高個案繼續懷孕的意願。另外,針對鑲嵌比率低於30%的個案,我們建議以未培養的羊水細胞進行微陣列分析,以避免因為培養造成偽陰性的結果。

Amniocentesis is a very common and effective tool for prenatal diagnosis of chromosomal abnormalities, whereas marker chromosomes are very rare chromosomal abnormalities. They may come from any region of any chromosome and the phenotypic variations are very tremendous. However, the genetic counseling of marker chromosomes becomes very difficult in prenatal diagnosis because of lacking rapid and effective molecular diagnostic methods that can clarify and characterize the marker chromosomes.
Chromosomal microarray comparative genomic hybridization (aCGH) uses two genomes (test and control), which are differentially labeled, and competitively hybridized to metaphase chromosomes. The fluorescent signal intensity of the labeled test DNA, relative to that of the control DNA, can then be linearly plotted across each chromosome for identification of changes on copy number. In this study, we collected a total of 68,087 cases of amniocentesis from January 2004 to December 2015. The chromosome aberration rate is 2.17% (1,478/68,087). In which, 59 cases were identified as small supernumerary marker chromosomes (sSMC), accounting for 0.087% (59/68,087) of the total collected cases. We performed chromosomal microarray CGH analysis in 45 of these 59 cases. Seven abnormal cases were found, with an abnormal rate of 16%, and comprising three cases of Cat Eye Syndrome, one case of Palister-Killian Syndrome, and one case of marker chromosome 15 syndrome. The other two marker chromosomes were derived from long arm of chromosome 11 and short arm of chromosome 12, respectively. But, the abnormal chromosome of case #8 (cell mosaic ratio 18.03%) was not found with the pathogenic gene gain via aCGH analysis. However, it may be a false negative case that was identified to be the iso(18p) by using fluorescence in situ hybridization.
Traditionally, the cytogenetic karyotyping is a gold standard technique for analysis of sSMC. Nevertheless, in our study, combining with aCGH analysis, pathogenic gene gains were found in 7 cases out of 45 cases. This result showed that aCGH analysis is possible to obtain information on whether there is a change on gene dose quickly and the possibility of gaining pathogenic genes. Such result provides a very informative reference for couples with sSMC in making decisions on continuing pregnancy which the gain of the pathogenic gene is not detected in de novo cases. In addition, for cases with a mosaic ratio of less than 30%, we recommend using uncultured amniocytes for aCGH analysis to avoid false negative results from cultured cells.
Rights: 同意授權瀏覽/列印電子全文服務,2020-08-10起公開。
Appears in Collections:獸醫學系所

Files in This Item:
File SizeFormat Existing users please Login
nchu-107-8101038003-1.pdf4.23 MBAdobe PDFThis file is only available in the university internal network    Request a copy
Show full item record

Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.