Microarrays, Postnatal Analysis, and Implications for Growth Monitoring

  • Aaron Theisen
  • Lisa G. Shaffer


Numerous genetic diseases associated with growth abnormalities result from cytogenetic aberrations. The development of microarray-based molecular cytogenetic techniques has enabled the identification of previously unrecognized genetic disorders, expanded the phenotypic spectrum, refined the critical regions of recognizable genetic disorders, and elucidated the etiologies of known clinical conditions. Comparative genomic hybridization (CGH)-based methodologies, which directly compare a patient to a control sample, are increasingly being used for clinical applications; numerous prospective studies show that CGH-based microarrays can identify unbalanced chromosome abnormalities in 12–18% of individuals with previous normal karyotyping analysis and idiopathic physical birth defects and/or developmental disabilities. More recently, single nucleotide polymorphism (SNP)-based microarrays, in which patient DNA is hybridized to a microarray and compared by computer analysis to a pool of normal individuals, have been introduced for clinical applications. SNP-based microarrays can detect, in addition to copy-number changes, loss of heterozygosity associated with uniparental disomies, nearly all of which are associated with growth abnormalities. Because these tests are not reliant on clinical suspicion of a specific condition, they provide an objective, comprehensive means of genetic diagnosis. In addition, because of their molecular-level resolution, microarrays have the potential to identify small abnormalities that may elucidate causative genes for clinical features and lead to the development of targeted gene therapies.


Chromosome Abnormality Comparative Genomic Hybridization Angelman Syndrome Single Nucleotide Polymorphism Array Uniparental Disomy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Microarray-based comparative genomic hybridization


Angelman syndrome


Bacterial artificial chromosome


Base pairs


Beckwith-Wiedemann syndrome


Comparative genomic hybridization


Copy-number neutral loss of heterozygosity


Fluorescence in situ hybridization


Global developmental delay


Intrauterine growth retardation


Thousand base pairs


Loss of heterozygosity


Million base pairs


Mental retardation


Prader–Willi syndrome


Single nucleotide polymorphism


Silver–Russell syndrome


Uniparental disomy


  1. Albertson DG, Ylstra B, Segraves R, Collins C, Dairkee SH, Kowbel D, Kuo WL, Gray JW, Pinkel D. Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene. Nat Genet. 2000;25:144–6.PubMedCrossRefGoogle Scholar
  2. Altherr MR, Wright TJ, Denison K, Perez-Castro AV, Johnson VP. Delimiting the Wolf-Hirschhorn syndrome critical region to 750 kilobase pairs. Am J Med Genet. 1997;71:47–53.PubMedCrossRefGoogle Scholar
  3. Amiel J, Espinosa-Parrilla Y, Steffann J, Gosset P, Pelet A, Prieur M, Boute O, Choiset A, Lacombe D, Philip N, Le Merrer M, Tanaka H, Till M, Touraine R, Toutain A, Vekemans M, Munnich A, Lyonnet S. Large-scale deletions and SMADIP1 truncating mutations in syndromic Hirschsprung disease with involvement of midline structures. Am J Hum Genet. 2001;69:1370–7.PubMedCrossRefGoogle Scholar
  4. Aston E, Whitby H, Maxwell T, Glaus N, Cowley B, Lowry D, Zhu XL, Issa B, South ST, Brothman AR. Comparison of targeted and whole genome analysis of postnatal specimens using a commercially available array based comparative genomic hybridisation (aCGH) microarray platform. J Med Genet. 2008;45:268–74.PubMedCrossRefGoogle Scholar
  5. Battaglia A, Carey JC, Wright TJ. Wolf-Hirschhorn (4p-) syndrome. Adv Pediatr. 2001;48:75–113.PubMedGoogle Scholar
  6. Biesecker LG. The end of the beginning of chromosome ends. Am J Med Genet. 2002;107:263–6.PubMedCrossRefGoogle Scholar
  7. Bischoff FZ, Feldman GL, McCaskill C, Subramanian S, Hughes MR, Shaffer LG. Single cell analysis demonstrating somatic mosaicism involving 11p in a patient with paternal isodisomy and Beckwith-Wiedemann syndrome. Hum Mol Genet. 1995;4:395–9.PubMedCrossRefGoogle Scholar
  8. Buxbaum JD, Cai G, Chaste P, Nygren G, Goldsmith J, Reichert J, Anckarsater H, Rastam M, Smith CJ, Silverman JM, Hollander E, Leboyer M, Gillberg C, Verloes A, Betancur C. Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:484–91.Google Scholar
  9. Cassidy SB. Prader-Willi syndrome. Curr Probl Pediatr. 1984;14:1–55.PubMedCrossRefGoogle Scholar
  10. Dastot-Le Moal F, Wilson M, Mowat D, Collot N, Niel F, Goossens M. ZFHX1B mutations in patients with Mowat-Wilson syndrome. Hum Mutat. 2007;28:313–21.PubMedCrossRefGoogle Scholar
  11. De Pater JM, Ippel PF, Bijlsma JB, Van Nieuwenhuizen O. Interstitial deletion 11q. Case report and review of the literature. Genet Couns. 1997;8:335–9.PubMedGoogle Scholar
  12. de Vries BB, Pfundt R, Leisink M, Koolen DA, Vissers LE, Janssen IM, Reijmersdal S, Nillesen WM, Huys EH, Leeuw N, Smeets D, Sistermans EA, Feuth T, Van Ravenswaaij-Arts CM, Van Kessel AG, Schoenmakers EF, Brunner HG, Veltman JA. Diagnostic genome profiling in mental retardation. Am J Hum Genet. 2005;77:606–16.PubMedCrossRefGoogle Scholar
  13. DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA, Trent JM. Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet. 1996;14:457–60.PubMedCrossRefGoogle Scholar
  14. Descipio C, Kaur M, Yaeger D, Innis JW, Spinner NB, Jackson LG, Krantz ID. Chromosome rearrangements in cornelia de Lange syndrome (CdLS): report of a der(3)t(3;12)(p25.3;p13.3) in two half sibs with features of CdLS and review of reported CdLS cases with chromosome rearrangements. Am J Med Genet A. 2005;137:276–82.Google Scholar
  15. Faivre L, Gosset P, Cormier-Daire V, Odent S, Amiel J, Giurgea I, Nassogne MC, Pasquier L, Munnich A, Romana S, Prieur M, Vekemans M, De Blois MC, Turleau C. Overgrowth and trisomy 15q26.1-qter including the IGF1 receptor gene: report of two families and review of the literature. Eur J Hum Genet. 2002;10:699–706.PubMedCrossRefGoogle Scholar
  16. Flint J, Wilkie AO, Buckle VJ, Winter RM, Holland AJ, McDermid HE. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet. 1995;9:132–40.PubMedCrossRefGoogle Scholar
  17. Friedman JM, Baross A, Delaney AD, Ally A, Arbour L, Asano J, Bailey DK, Barber S, Birch P, Brown-John M, Cao M, Chan S, Charest DL, Farnoud N, Fernandes N, Flibotte S, Go A, Gibson WT, Holt RA, Jones SJ, Kennedy GC, Krzywinski M, Langlois S, Li HI, McGillivray BC, Nayar T, Pugh TJ, Rajcan-Separovic E, Schein JE, Schnerch A, Siddiqui A, Van Allen MI, Wilson G, Yong SL, Zahir F, Eydoux P, Marra MA. Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation. Am J Hum Genet. 2006;79:500–13.PubMedCrossRefGoogle Scholar
  18. Gillis LA, McCallum J, Kaur M, Descipio C, Yaeger D, Mariani A, Kline AD, Li HH, Devoto M, Jackson LG, Krantz ID. NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations. Am J Hum Genet. 2004;75:610–23.PubMedCrossRefGoogle Scholar
  19. Greenberg F, Guzzetta V, Montes De Oca-Luna R, Magenis RE, Smith AC, Richter SF, Kondo I, Dobyns WB, Patel PI, Lupski JR. Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2). Am J Hum Genet. 1991;49:1207–18.PubMedGoogle Scholar
  20. Grossfeld PD, Mattina T, Lai Z, Favier R, Jones KL, Cotter F, Jones C. The 11q terminal deletion disorder: a prospective study of 110 cases. Am J Med Genet A. 2004;129A:51–61.PubMedCrossRefGoogle Scholar
  21. Hammond LS, Macias MM, Tarleton JC, Shashidhar Pai G. Fragile X syndrome and deletions in FMR1: new case and review of the literature. Am J Med Genet. 1997;72:430–4.PubMedCrossRefGoogle Scholar
  22. Harris J, Robert E, Kallen B. Epidemiology of choanal atresia with special reference to the CHARGE association. Pediatrics. 1997;99:363–7.PubMedCrossRefGoogle Scholar
  23. Heilstedt HA, Ballif BC, Howard LA, Kashork CD, Shaffer LG. Population data suggest that deletions of 1p36 are a relatively common chromosome abnormality. Clin Genet. 2003a;64:310–6.PubMedCrossRefGoogle Scholar
  24. Heilstedt HA, Ballif BC, Howard LA, Lewis RA, Stal S, Kashork CD, Bacino CA, Shapira SK, Shaffer LG. Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome. Am J Hum Genet. 2003b;72:1200–12.PubMedCrossRefGoogle Scholar
  25. Henry I, Bonaiti-Pellie C, Chehensse V, Beldjord C, Schwartz C, Utermann G, Junien C. Uniparental paternal disomy in a genetic cancer-predisposing syndrome. Nature. 1991;351:665–7.PubMedCrossRefGoogle Scholar
  26. Ishihara N, Yamada K, Yamada Y, Miura K, Kato J, Kuwabara N, Hara Y, Kobayashi Y, Hoshino K, Nomura Y, Mimaki M, Ohya K, Matsushima M, Nitta H, Tanaka K, Segawa M, Ohki T, Ezoe T, Kumagai T, Onuma A, Kuroda T, Yoneda M, Yamanaka T, Saeki M, Saji T, Nagaya M, Wakamatsu N. Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22–q24.1. J Med Genet. 2004;41:387–93.PubMedCrossRefGoogle Scholar
  27. Kallen B, Tornqvist K. The epidemiology of anophthalmia and microphthalmia in Sweden. Eur J Epidemiol. 2005;20:345–50.PubMedCrossRefGoogle Scholar
  28. Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992;258:818–21.PubMedCrossRefGoogle Scholar
  29. Knight SJ, Regan R, Nicod A, Horsley SW, Kearney L, Homfray T, Winter RM, Bolton P, Flint J. Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet. 1999;354:1676–81.PubMedCrossRefGoogle Scholar
  30. Krantz ID, McCallum J, Descipio C, Kaur M, Gillis LA, Yaeger D, Jukofsky L, Wasserman N, Bottani A, Morris CA, Nowaczyk MJ, Toriello H, Bamshad MJ, Carey JC, Rappaport E, Kawauchi S, Lander AD, Calof AL, Li HH, Devoto M, Jackson LG. Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B. Nat Genet. 2004;36:631–5.PubMedCrossRefGoogle Scholar
  31. Krepischi-Santos AC, Vianna-Morgante AM, Jehee FS, Passos-Bueno MR, Knijnenburg J, Szuhai K, Sloos W, Mazzeu JF, Kok F, Cheroki C, Otto PA, Mingroni-Netto RC, Varela M, Koiffmann C, Kim CA, Bertola DR, Pearson PL, Rosenberg C. Whole-genome array-CGH screening in undiagnosed syndromic patients: old syndromes revisited and new alterations. Cytogenet Genome Res. 2006;115:254–61.PubMedCrossRefGoogle Scholar
  32. Kurotaki N, Harada N, Shimokawa O, Miyake N, Kawame H, Uetake K, Makita Y, Kondoh T, Ogata T, Hasegawa T, Nagai T, Ozaki T, Touyama M, Shenhav R, Ohashi H, Medne L, Shiihara T, Ohtsu S, Kato Z, Okamoto N, Nishimoto J, Lev D, Miyoshi Y, Ishikiriyama S, Sonoda T, Sakazume S, Fukushima Y, Kurosawa K, Cheng JF, Yoshiura K, Ohta T, Kishino T, Niikawa N, Matsumoto N. Fifty microdeletions among 112 cases of Sotos syndrome: low copy repeats possibly mediate the common deletion. Hum Mutat. 2003;22:378–87.PubMedCrossRefGoogle Scholar
  33. Kuwano A, Mutirangura A, Dittrich B, Buiting K, Horsthemke B, Saitoh S, Niikawa N, Ledbetter SA, Greenberg F, Chinault AC, et al. Molecular dissection of the Prader-Willi/Angelman syndrome region (15q11–13) by YAC cloning and FISH analysis. Hum Mol Genet. 1992;1:417–25.PubMedCrossRefGoogle Scholar
  34. Lindlof M, Kaariainen H, Van Ommen GJ, De La Chapelle A. Microdeletions in patients with X-linked muscular dystrophy: molecular-clinical correlations. Clin Genet. 1988;33:131–9.PubMedCrossRefGoogle Scholar
  35. Lowery MC, Morris CA, Ewart A, Brothman LJ, Zhu XL, Leonard CO, Carey JC, Keating M, Brothman AR. Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: evaluation of 235 patients. Am J Hum Genet. 1995;57:49–53.PubMedGoogle Scholar
  36. Lu X, Shaw CA, Patel A, Li J, Cooper ML, Wells WR, Sullivan CM, Sahoo T, Yatsenko SA, Bacino CA, Stankiewicz P, Ou Z, Chinault AC, Beaudet AL, Lupski JR, Cheung SW, Ward PA. Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases. PLoS ONE. 2007;2:e327.PubMedCrossRefGoogle Scholar
  37. Lucito R, Healy J, Alexander J, Reiner A, Esposito D, Chi M, Rodgers L, Brady A, Sebat J, Troge J, West JA, Rostan S, Nguyen KC, Powers S, Ye KQ, Olshen A, Venkatraman E, Norton L, Wigler M. Representational oligonucleotide microarray analysis: a high-resolution method to detect genome copy number variation. Genome Res. 2003;13:2291–305.PubMedCrossRefGoogle Scholar
  38. Magenis RE, Toth-Fejel S, Allen LJ, Black M, Brown MG, Budden S, Cohen R, Friedman JM, Kalousek D, Zonana J, et al. Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: specific regions, extent of deletions, parental origin, and clinical consequences. Am J Med Genet. 1990;35:333–49.PubMedCrossRefGoogle Scholar
  39. Malan V, Chevallier S, Soler G, Coubes C, Lacombe D, Pasquier L, Soulier J, Morichon-Delvallez N, Turleau C, Munnich A, Romana S, Vekemans M, Cormier-Daire V, Colleaux L. Array-based comparative genomic hybridization identifies a high frequency of copy number variations in patients with syndromic overgrowth. Eur J Hum Genet. 2010;18:227–32.Google Scholar
  40. Mariani S, Iughetti L, Bertorelli R, Coviello D, Pellegrini M, Forabosco A, Bernasconi S. Genotype/phenotype correlations of males affected by Simpson-Golabi-Behmel syndrome with GPC3 gene mutations: patient report and review of the literature. J Pediatr Endocrinol Metab. 2003;16:225–32.PubMedCrossRefGoogle Scholar
  41. Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PLM, Zheng Z, Liaw D, Caron S, Duboué B, Lin AY, Richardson A-L, Bonnetblanc J-M, Bressieux J-M, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker J-P, Gorlin RJ, Hodgson SV, Huson S, Lacombe D, LePrat F, Odent S, Toulouse C, Olopade OI, Sobol H, Tishler S, Woods CG, Robinson BG, Weber HC, Parsons R, Peacocke M, Longy M, Eng C. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet. 1998;7:507–15.Google Scholar
  42. McMullan DJ, Bonin M, Hehir-Kwa JY, De Vries BB, Dufke A, Rattenberry E, Steehouwer M, Moruz L, Pfundt R, De Leeuw N, Riess A, Altug-Teber O, Enders H, Singer S, Grasshoff U, Walter M, Walker JM, Lamb CV, Davison EV, Brueton L, Riess O, Veltman JA. Molecular karyotyping of patients with unexplained mental retardation by SNP arrays: a multicenter study. Hum Mutat. 2009;30:1082–92.PubMedCrossRefGoogle Scholar
  43. Mencarelli MA, Katzaki E, Papa FT, Sampieri K, Caselli R, Uliana V, Pollazzon M, Canitano R, Mostardini R, Grosso S, Longo I, Ariani F, Meloni I, Hayek J, Balestri P, Mari F, Renieri A. Private inherited microdeletion/microduplications: implications in clinical practice. Eur J Med Genet. 2008;51:409–16.PubMedCrossRefGoogle Scholar
  44. Ming JE, Geiger E, James AC, Ciprero KL, Nimmakayalu M, Zhang Y, Huang A, Vaddi M, Rappaport E, Zackai EH, Shaikh TH. Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays. Hum Mutat. 2006;27:467–73.PubMedCrossRefGoogle Scholar
  45. Moore T, Haig D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet. 1991;7:45–9.PubMedGoogle Scholar
  46. Nagai T, Shimokawa O, Harada N, Sakazume S, Ohashi H, Matsumoto N, Obata K, Yoshino A, Murakami N, Murai T, Sakuta R, Niikawa N. Postnatal overgrowth by 15q-trisomy and intrauterine growth retardation by 15q-monosomy due to familial translocation t(13;15): dosage effect of IGF1R? Am J Med Genet. 2002;113:173–7.PubMedCrossRefGoogle Scholar
  47. Neill NJ, Torchia BS, Bejjani BA, Shaffer LG, Ballif BC. Comparative analysis of copy number detection by whole-genome BAC and oligonucleotide array CGH. Mol Cytogenet. 2010;3:11.PubMedCrossRefGoogle Scholar
  48. Nicholls RD, Knoll JH, Butler MG, Karam S, Lalande M. Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature. 1989;342:281–5.PubMedCrossRefGoogle Scholar
  49. Nickerson E, Greenberg F, Keating MT, McCaskill C, Shaffer LG. Deletions of the elastin gene at 7q11.23 occur in approximately 90% of patients with Williams syndrome. Am J Hum Genet. 1995;56:1156–61.PubMedGoogle Scholar
  50. Niemitz EL, Debaun MR, Fallon J, Murakami K, Kugoh H, Oshimura M, Feinberg AP. Microdeletion of LIT1 in familial Beckwith-Wiedemann syndrome. Am J Hum Genet. 2004;75:844–9.PubMedCrossRefGoogle Scholar
  51. Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D, Collins C, Kuo WL, Chen C, Zhai Y, Dairkee SH, Ljung BM, Gray JW, Albertson DG. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet. 1998;20:207–11.PubMedCrossRefGoogle Scholar
  52. Quan F, Zonana J, Gunter K, Peterson KL, Magenis RE, Popovich BW. An atypical case of fragile X syndrome caused by a deletion that includes the FMR1 gene. Am J Hum Genet. 1995;56:1042–51.PubMedGoogle Scholar
  53. Schena M, Shalon D, Davis RW, Brown PO. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. 1995;270:467–70.PubMedCrossRefGoogle Scholar
  54. Shaffer LG, Lupski JR. Molecular mechanisms for constitutional chromosomal rearrangements in humans. Annu Rev Genet. 2000;34:297–329.PubMedCrossRefGoogle Scholar
  55. Shaffer LG, Bejjani BA, Torchia B, Kirkpatrick S, Coppinger J, Ballif BC. The identification of microdeletion syndromes and other chromosome abnormalities: cytogenetic methods of the past, new technologies for the future. Am J Med Genet C Semin Med Genet. 2007a;145C:335–45.PubMedCrossRefGoogle Scholar
  56. Shaffer LG, Theisen A, Bejjani BA, Ballif BC, Aylsworth AS, Lim C, McDonald M, Ellison JW, Kostiner D, Saitta S, Shaikh T. The discovery of microdeletion syndromes in the post-genomic era: review of the methodology and characterization of a new 1q41q42 microdeletion syndrome. Genet Med. 2007b;9:607–16.PubMedCrossRefGoogle Scholar
  57. Shaikh TH. Oligonucleotide arrays for high-resolution analysis of copy number alteration in mental retardation/multiple congenital anomalies. Genet Med. 2007;9:617–25.PubMedCrossRefGoogle Scholar
  58. Sharp AJ, Hansen S, Selzer RR, Cheng Z, Regan R, Hurst JA, Stewart H, Price SM, Blair E, Hennekam RC, Fitzpatrick CA, Segraves R, Richmond TA, Guiver C, Albertson DG, Pinkel D, Eis PS, Schwartz S, Knight SJ, Eichler EE. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat Genet. 2006;38:1038–42.PubMedCrossRefGoogle Scholar
  59. Shevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtz D, Majnemer A, Noetzel M, Sheth RD. 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;60:367–80.PubMedGoogle Scholar
  60. Slager RE, Newton TL, Vlangos CN, Finucane B, Elsea SH. Mutations in RAI1 associated with Smith-Magenis syndrome. Nat Genet. 2003;33:466–8.PubMedCrossRefGoogle Scholar
  61. Solinas-Toldo S, Lampel S, Stilgenbauer S, Nickolenko J, Benner A, Dohner H, Cremer T, Lichter P. Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer. 1997;20:399–407.PubMedCrossRefGoogle Scholar
  62. Tatton-Brown K, Douglas J, Coleman K, Baujat G, Chandler K, Clarke A, Collins A, Davies S, Faravelli F, Firth H, Garrett C, Hughes H, Kerr B, Liebelt J, Reardon W, Schaefer GB, Splitt M, Temple IK, Waggoner D, Weaver DD, Wilson L, Cole T, Cormier-Daire V, Irrthum A, Rahman N. Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome. J Med Genet. 2005;42:307–13.PubMedCrossRefGoogle Scholar
  63. Thuresson AC, Bondeson ML, Edeby C, Ellis P, Langford C, Dumanski JP, Anneren G. Whole-genome array-CGH for detection of submicroscopic chromosomal imbalances in children with mental retardation. Cytogenet Genome Res. 2007;118:1–7.PubMedCrossRefGoogle Scholar
  64. Tolarova MM, Cervenka J. Classification and birth prevalence of orofacial clefts. Am J Med Genet. 1998;75:126–37.PubMedCrossRefGoogle Scholar
  65. Tunnacliffe A, Jones C, Le Paslier D, Todd R, Cherif D, Birdsall M, Devenish L, Yousry C, Cotter FE, James MR. Localization of Jacobsen syndrome breakpoints on a 40-Mb physical map of distal chromosome 11q. Genome Res. 1999;9:44–52.PubMedGoogle Scholar
  66. Turkmen S, Gillessen-Kaesbach G, Meinecke P, Albrecht B, Neumann LM, Hesse V, Palanduz S, Balg S, Majewski F, Fuchs S, Zschieschang P, Greiwe M, Mennicke K, Kreuz FR, Dehmel HJ, Rodeck B, Kunze J, Tinschert S, Mundlos S, Horn D. Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes. Eur J Hum Genet. 2003;11:858–65.PubMedCrossRefGoogle Scholar
  67. Van Buggenhout G, Melotte C, Dutta B, Froyen G, Van Hummelen P, Marynen P, Matthijs G, De Ravel T, Devriendt K, Fryns JP, Vermeesch JR. Mild Wolf-Hirschhorn syndrome: micro-array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype-phenotype map. J Med Genet. 2004;41:691–8.PubMedCrossRefGoogle Scholar
  68. Voskova-Goldman A, Peier A, Caskey CT, Richards CS, Shaffer LG. DMD-specific FISH probes are diagnostically useful in the detection of female carriers of DMD gene deletions. Neurology. 1997;48:1633–8.PubMedGoogle Scholar
  69. Wagenstaller J, Spranger S, Lorenz-Depiereux B, Kazmierczak B, Nathrath M, Wahl D, Heye B, Glaser D, Liebscher V, Meitinger T, Strom TM. Copy-number variations measured by single-nucleotide-polymorphism oligonucleotide arrays in patients with mental retardation. Am J Hum Genet. 2007;81:768–79.PubMedCrossRefGoogle Scholar
  70. Waggoner DJ, Raca G, Welch K, Dempsey M, Anderes E, Ostrovnaya I, Alkhateeb A, Kamimura J, Matsumoto N, Schaeffer GB, Martin CL, Das S. NSD1 analysis for Sotos syndrome: insights and perspectives from the clinical laboratory. Genet Med. 2005;7:524–33.PubMedCrossRefGoogle Scholar
  71. Yu W, Ballif BC, Kashork CD, Heilstedt HA, Howard LA, Cai WW, White LD, Liu W, Beaudet AL, Bejjani BA, Shaw CA, Shaffer LG. Development of a comparative genomic hybridization microarray and demonstration of its utility with 25 well-characterized 1p36 deletions. Hum Mol Genet. 2003;12:2145–52.PubMedCrossRefGoogle Scholar
  72. Zhou XP, Waite KA, Pilarski R, Hampel H, Fernandez MJ, Bos C, Dasouki M, Feldman GL, Greenberg LA, Ivanovich J, Matloff E, Patterson A, Pierpont ME, Russo D, Nassif NT, Eng C. Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. Am J Hum Genet. 2003;73:404–11.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Signature Genomic LaboratoriesSpokaneUSA

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