The Journal of Pediatrics
Volume 155, Issue 3 , Pages 311-317 , September 2009

Clinical Application of Microarray-Based Molecular Cytogenetics: An Emerging New Era of Genomic Medicine

  • Marilyn M. Li, MD

      Affiliations

    • Hayward Genetics Center and the Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA
    • Corresponding Author InformationReprint requests: Marilyn Li, MD, Hayward Genetics Center, Tulane University Medical School, 1430 Tulane Ave., SL-31, New Orleans LA 70112.
    • ,
  • Hans C. Andersson, MD

      Affiliations

    • Hayward Genetics Center and the Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA

Received 23 October 2008 ,Revised 24 February 2009 ,Accepted 1 April 2009.

References 

  1. Lejeune J, Turpin R. Chromosomal aberrations in man. Am J Hum Genet. 1961;13:175–184
  2. Nowell PC, Hungerford DA. A minute chromosome in human chronic granulocytic leukemia. Science. 1960;132:1488–1501
  3. Caspersson T, Zech L, Johansson C, Modest EJ. Identification of human chromosomes by DNA-binding fluorescent agents. Chromosoma. 1970;30:215–227
  4. Lichter P, Ward DC. Is non-isotopic in-situ hybridization finally coming of age?. Nature. 1990;338:348–350
  5. Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D, et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet. 1998;20:207–211
  6. Lee C, Iafrate A, Brothman A. Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nat Genet. 2007;39:S48–S54
  7. Feuk L, Carson AR, Scherer SW. Structural variation in the human genome. Nat Rev Genet. 2006;7:85–97
  8. Shevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtz D, et al. Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2003;60:367–380
  9. Ravnan JB, Tepperberg JH, Papenhausen P, Lamb AN, Hedrick J, Eash D, et al. Subtelomere FISH analysis of 11 688 cases: an evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities. J Med Genet. 2006;43:478–489
  10. Lu XY, Phung MT, Shaw CA, Pham K, Neil SE, Patel A, et al. Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis. Pediatrics. 2008;122:1310–1318
  11. Li M, Budarf ML, Chien P, Barnoski BL, Emanuel BS, Driscoll DA. Clustering of DiGeorge/Velocardiofacial-associated translocations suggestive of translocation “hot spots”. Am J Human Genet. 1995;57:A119
  12. Ou Z, Berg JS, Yonath H, Enciso VB, Miller DT, Picker J, et al. Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes. Genet Med. 2008;10:267–277
  13. Lupski JR. Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet. 1998;14:417–422
  14. Korbel JO, Urban AE, Affourtit JP, Godwin B, Grubert F, Simons JF, et al. Paired-end mapping reveals extensive structural variation in the human genome. Science. 2007;318:420–426
  15. Li MM, Nimmakayalu MA, Mercer D, Andersson H, Emanuel BS. Characterization of a cryptic 3.3 Mb deletion in a patient with a “balanced t(15;22) translocation” using high density oligo arrayCGH and gene expression arrays. Am J Med Genet. 2008;146:368–375
  16. Driscoll DA, Li M, Chien P, Capuano S, Zackai EH, McDonald-McGinn DM, et al. Familial 22q11 Deletion: phenotypic variability and determination of deletion boundaries by FISH. Am J Human Genet. 1995;57:A33
  17. Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet. 1997;15:70–73
  18. Slager RE, Newton TL, Vlangos CN. Finucane, Elsea SH. Mutations in RAI1 associated with Smith-Magenis syndrome. Nat Genet. 2003;33:466–468
  19. Kurotaki N, Harada N, Shimokawa O, Miyake N, Kawame H, Uetake K, et al. Fifty microdeletions among 112 cases of Sotos syndrome: low copy repeats possibly mediate the common deletion. Hum Mutat. 2003;22:378–387
  20. Crolla JA. van HV. Frequent chromosome aberrations revealed by molecular cytogenetic studies in patients with aniridia. Am J Hum Genet. 2002;71:1138–1149
  21. Johnson D, Horsley SM, Moloney DM, Oldridge M, Twigg SR, Walsh S, et al. A comprehensive screen for TWIST mutations in patients with craniosynostosis identifies a new microdeletion syndrome of chromosome band 7p21.1. Am J Hum Genet. 1998;63:1282–1293
  22. Vissers LE, Veltman JA, van Kessel AG, Brunner HG. Identification of disease genes by whole genome CGH arrays. Hum Mol Genet. 2005;14:R215–R223
  23. Davenport SLH, Hefner MA, Mitchell JA. The spectrum of clinical features in CHARGE syndrome. Clin Genet. 1986;29:298–310
  24. Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de Vries BB, Janssen IM, et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. 2004;36:955–957
  25. Saitsu H, Kato M, Mizuguchi T, Hamada K, Osaka H, Tohyama J, et al. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet. 2008;40:782–788
  26. Lesnik Oberstein SA, Kriek M, White SJ, Kalf ME, Szuhai K, den Dunnen JT, et al. Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase. Am J Hum Genet. 2006;79:562–566
  27. Grzeschik KH, Bornholdt D, Oeffner F, König A, del Carmen Boente M, Enders H, et al. Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia. Nat Genet. 2007;39:833–835
  28. Unger S, Böhm D, Kaiser FJ, Kaulfuss S, Borozdin W, Buiting K, et al. Mutations in the cyclin family member FAM58A cause an X-linked dominant disorder characterized by syndactyly, telecanthus and anogenital and renal malformations. Nat Genet. 2008;40:287–289
  29. Slavotinek AM. Novel microdeletion syndromes detected by chromosome microarrays. Hum Genet. 2008;124:1–17
  30. Ledbetter DH. Cytogenetic Technology—Genotype and Phenotype. N Engl J Med. 2008;359:1728–1730
  31. Mefford H, Sharp A, Baker C, Itsara A, Jiang Z, Buysse K, et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N Engl J Med. 2008;359:1685–1699
  32. Shaffer LG, Theisen A, Bejjani BA, Ballif BC, Aylsworth AS, Lim C, et al. The discovery of microdeletion syndromes in the postgenomic era: review of the methodology and characterization of a new 1q41q42 microdeletion syndrome. Genet Med. 2007;9:607–616
  33. Rajcan-Separovic E, Harvard C, Liu X, McGillivray B, Hall JG, Qiao Y, et al. Clinical and molecular cytogenetic characterization of a newly recognised microdeletion syndrome involving 2p15-16.1. J Med Genet. 2007;44:269–276
  34. Lisi EC, Hamosh A, Doheny KF, Squibb E, Jackson B, Galczynski R, et al. 3q29 interstitial microduplication: a new syndrome in a three-generation family. Am J Med Genet A. 2008;146:601–609
  35. Somerville MJ, Mervis CB, Young EJ, Seo EJ, del Campo M, Bamforth S, et al. Severe expressive-language delay related to duplication of the Williams-Beuren locus. N Engl J Med. 2005;353:1694–1701
  36. Shieh JT, Aradhya S, Novelli A, Manning MA, Cherry AM, Brumblay J, et al. Nablus mask-like facial syndrome is caused by a microdeletion of 8q detected by array-based comparative genomic hybridization. Am J Med Genet A. 2006;140:1267–1273
  37. Redon R, Baujat G, Sanlaville D, Le Merrer M, Vekemans M, Munnich A, et al. Interstitial 9q22.3 microdeletion: clinical and molecular characterization of a newly recognised overgrowth syndrome. Eur J Hum Genet. 2006;14:759–767
  38. Sharp AJ, Mefford HC, Li K, Baker C, Skinner C, Stevenson RE, et al. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat Genet. 2008;40:322–328
  39. Sharp AJ, Selzer RR, Veltman JA, Gimelli S, Gimelli G, Striano P, et al. Characterization of a recurrent 15q24 microdeletion syndrome. Hum Mol Genet. 2007;16:567–572
  40. Ballif BC, Hornor SA, Jenkins E, Madan-Khetarpal S, Surti U, Jackson KE, et al. Discovery of a previously unrecognized microdeletion syndrome of 16p11.2-p12.2. Nat Genet. 2007;39:1071–1073
  41. Potocki L, Bi W, Treadwell-Deering D, Carvalho CM, Eifert A, Friedman EM, et al. Characterization of Potocki-Lupski syndrome [dup(17)(p11.2p11. 2)] and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Am J Hum Genet. 2007;80:633–649
  42. Brunetti-Pierri N, Grange DK, Ou Z, Peiffer DA, Peacock SK, Cooper ML, et al. Characterization of de novo microdeletions involving 17q11.2q12 identified through chromosomal comparative genomic hybridization. Clin Genet. 2007;72:411–419
  43. Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R, Kapur R, et al. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am J Hum Genet. 2007;81:1057–1069
  44. Koolen DA, Vissers LE, Pfundt R, de Leeuw N, Knight SJ, Regan R, et al. A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism. Nat Genet. 2006;38:999–1001
  45. Borozdin W, Graham JM, Böhm D, Bamshad MJ, Spranger S, Burke L, et al. Multigene deletions on chromosome 20q13.13-q13.2 including SALL4 result in an expanded phenotype of Okihiro syndrome plus developmental delay. Hum Mutat. 2007;28:830
  46. Shinawi M, Erez A, Shardy DL, Lee B, Naeem R, Weissenberger G, et al. Syndromic thrombocytopenia and predisposition to acute myelogenous leukemia caused by constitutional microdeletions on chromosome 21q. Blood. 2008;12:1042–1047
  47. Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, Hollanders K, et al. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet. 2005;77:442–453
  48. Bergamaschi A, Kim YH, Wang P, Sorlie T, Hernandez-Boussard T, Lonning PE, et al. Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Gene Chromosome Canc. 2006;45:1033–1040
  49. Carrasco DR, Tonon G, Huang Y, Zhang Y, Sinha R, Feng B, et al. High resolution genomic profiles define distinct clinicopathogenetic subgroups of multiple myeloma patients. Cancer Cell. 2006;9:313–325
  50. Suela J, Alvarez S, Cifuentes F, Largo C, Ferreira BI, Blesa D, et al. DNA profiling analysis of 100 consecutive de novo acute myeloid leukemia cases reveals patterns of genomic instability that affect all cytogenetic risk groups. Leukemia. 2007;21:1224–1231
  51. Tagawa H, Suguro M, Tsuzuki S, Matsuo K, Karnan S, Ohshima K, et al. Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma. Blood. 2005;106:1770–1777
  52. Birrer MJ, Johnson ME, Hao K, Wong KK, Park DC, Bell A, et al. Whole genome oligonucleotide-based array comparative genomic hybridization analysis identified fibroblast growth factor 1 as a prognostic marker for advanced-stage serous ovarian adenocarcinomas. J Clin Oncol. 2007;25:2281–2287
  53. Meshinchi S, Alonzo TA, Stirewalt DL, Zwaan M, Zimmerman M, Reinhardt D, et al. Clinical implications of FLT3 mutations in pediatric AML. Blood. 2006;108:3654–3661
  54. Stone RM, DeAngelo DJ, Klimek V, Galinsky I, Estey E, Nimer SD, et al. Acute myeloid leukemia patients with an activating mutation in FLT3 respond to a small molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood. 2005;105:54–60
  55. Staaf J, Törngren T, Rambech E, Johansson U, Persson C, Sellberg G, et al. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH). Hum Mutat. 2008;29:555–564
  56. Picelli S, Vandrovcova J, Jones S, Djureinovic T, Skoglund J, Zhou XL, et al. Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q. BMC Cancer. 2008;8:87
  57. Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerriere A, et al. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet. 2006;38:24–26
  58. Nishioka K, Hayashi S, Farrer MJ, Singleton AB, Yoshino H, et al. Clinical heterogeneity of α-synuclein gene duplication in Parkinson's disease. Ann Neurol. 2006;59:298–309
  59. Fellermann K, Stange DE, Schaeffeler E, Schmalzl H, Wehkamp J, Bevins CL, et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet. 2006;79:439–448
  60. Gonzalez E, Kulkarni H, Bolivar H, Mangano A, Sanchez R, Catano G, et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science. 2005;307:1422–1424
  61. Mikhailovich V, Gryadunov D, Kolchinsky A, Makarov A, Zasedatelev A. DNA microarrays in the clinic: infectious diseases. BioEssays. 2008;30:673–682
  62. Van den Veyver IB, Beaudet AL. Comparative genomic hybridization and prenatal diagnosis. Curr Opin Obstet Gynecol. 2006;18:185–191

 The authors declare no conflicts of interest, real or perceived.

PII: S0022-3476(09)00358-8

doi: 10.1016/j.jpeds.2009.04.001

The Journal of Pediatrics
Volume 155, Issue 3 , Pages 311-317 , September 2009

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