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. 2001 Nov;38(11):740–744. doi: 10.1136/jmg.38.11.740

High resolution comparative genomic hybridisation in clinical cytogenetics

M Kirchhoff 1, H Rose 1, C Lundsteen 1
PMCID: PMC1734756  PMID: 11694545

Abstract

High resolution comparative genomic hybridisation (HR-CGH) is a diagnostic tool in our clinical cytogenetics laboratory. The present survey reports the results of 253 clinical cases in which 47 abnormalities were detected. Among 144 dysmorphic and mentally retarded subjects with a normal conventional karyotype, 15 (10%) had small deletions or duplications, of which 11 were interstitial. In addition, a case of mosaic trisomy 9 was detected. Among 25 dysmorphic and mentally retarded subjects carrying apparently balanced de novo translocations, four had deletions at translocation breakpoints and two had deletions elsewhere in the genome. Seventeen of 19 complex rearrangements were clarified by HR-CGH. A small supernumerary marker chromosome occurring with low frequency and the breakpoint of a mosaic r(18) case could not be clarified. Three of 19 other abnormalities could not be confirmed by HR-CGH. One was a Williams syndrome deletion and two were DiGeorge syndrome deletions, which were apparently below the resolution of HR-CGH. However, we were able to confirm Angelman and Prader-Willi syndrome deletions, which are about 3-5 Mb. We conclude that HR-CGH should be used for the evaluation of (1) dysmorphic and mentally retarded subjects where normal karyotyping has failed to show abnormalities, (2) dysmorphic and mentally retarded subjects carrying apparently balanced de novo translocations, (3) apparently balanced de novo translocations detected prenatally, and (4) for clarification of complex structural rearrangements.


Keywords: comparative genomic hybridisation; chromosome analysis; chromosome aberrations; dysmorphism

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Selected References

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  1. Aviram-Goldring A., Fritz B., Bartsch C., Steuber E., Daniely M., Lev D., Chaki R., Barkai G., Frydman M., Rehder H. Molecular cytogenetic studies in three patients with partial trisomy 2p, including CGH from paraffin-embedded tissue. Am J Med Genet. 2000 Mar 6;91(1):74–82. doi: 10.1002/(sici)1096-8628(20000306)91:1<74::aid-ajmg14>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  2. Barber J. C., Cross I. E., Douglas F., Nicholson J. C., Moore K. J., Browne C. E. Neurofibromatosis pseudogene amplification underlies euchromatic cytogenetic duplications and triplications of proximal 15q. Hum Genet. 1998 Nov;103(5):600–607. doi: 10.1007/s004390050875. [DOI] [PubMed] [Google Scholar]
  3. Barber J. C., Reed C. J., Dahoun S. P., Joyce C. A. Amplification of a pseudogene cassette underlies euchromatic variation of 16p at the cytogenetic level. Hum Genet. 1999 Mar;104(3):211–218. doi: 10.1007/s004390050938. [DOI] [PubMed] [Google Scholar]
  4. Browne C. E., Dennis N. R., Maher E., Long F. L., Nicholson J. C., Sillibourne J., Barber J. C. Inherited interstitial duplications of proximal 15q: genotype-phenotype correlations. Am J Hum Genet. 1997 Dec;61(6):1342–1352. doi: 10.1086/301624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Christiaens G. C., Vissers J., Poddighe P. J., de Pater J. M. Comparative genomic hybridization for cytogenetic evaluation of stillbirth. Obstet Gynecol. 2000 Aug;96(2):281–286. doi: 10.1016/s0029-7844(00)00879-6. [DOI] [PubMed] [Google Scholar]
  6. Daniely M., Aviram-Goldring A., Barkai G., Goldman B. Detection of chromosomal aberration in fetuses arising from recurrent spontaneous abortion by comparative genomic hybridization. Hum Reprod. 1998 Apr;13(4):805–809. doi: 10.1093/humrep/13.4.805. [DOI] [PubMed] [Google Scholar]
  7. Daniely M., Barkai G., Goldman B., Aviram-Goldring A. Structural unbalanced chromosome rearrangements resolved by comparative genomic hybridization. Cytogenet Cell Genet. 1999;86(1):51–55. doi: 10.1159/000015409. [DOI] [PubMed] [Google Scholar]
  8. Flint J., Wilkie A. O., Buckle V. J., Winter R. M., Holland A. J., McDermid H. E. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet. 1995 Feb;9(2):132–140. doi: 10.1038/ng0295-132. [DOI] [PubMed] [Google Scholar]
  9. Kirchhoff M., Gerdes T., Maahr J., Rose H., Bentz M., Döhner H., Lundsteen C. Deletions below 10 megabasepairs are detected in comparative genomic hybridization by standard reference intervals. Genes Chromosomes Cancer. 1999 Aug;25(4):410–413. doi: 10.1002/(sici)1098-2264(199908)25:4<410::aid-gcc17>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  10. Kirchhoff M., Gerdes T., Maahr J., Rose H., Lundsteen C. Automatic correction of the interfering effect of unsuppressed interspersed repetitive sequences in comparative genomic hybridization analysis. Cytometry. 1997 Jun 1;28(2):130–134. [PubMed] [Google Scholar]
  11. Kirchhoff M., Gerdes T., Rose H., Maahr J., Ottesen A. M., Lundsteen C. Detection of chromosomal gains and losses in comparative genomic hybridization analysis based on standard reference intervals. Cytometry. 1998 Mar 1;31(3):163–173. [PubMed] [Google Scholar]
  12. Kirchhoff M., Rose H., Maahr J., Gerdes T., Bugge M., Tommerup N., Tümer Z., Lespinasse J., Jensen P. K., Wirth J. High resolution comparative genomic hybridisation analysis reveals imbalances in dyschromosomal patients with normal or apparently balanced conventional karyotypes. Eur J Hum Genet. 2000 Sep;8(9):661–668. doi: 10.1038/sj.ejhg.5200512. [DOI] [PubMed] [Google Scholar]
  13. Knight S. J., Flint J. Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis. J Med Genet. 2000 Jun;37(6):401–409. doi: 10.1136/jmg.37.6.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knight S. J., Regan R., Nicod A., Horsley S. W., Kearney L., Homfray T., Winter R. M., Bolton P., Flint J. Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet. 1999 Nov 13;354(9191):1676–1681. doi: 10.1016/S0140-6736(99)03070-6. [DOI] [PubMed] [Google Scholar]
  15. Lapierre J. M., Cacheux V., Collot N., Da Silva F., Hervy N., Rivet D., Romana S., Wiss J., Benzaken B., Aurias A. Comparison of comparative genomic hybridization with conventional karyotype and classical fluorescence in situ hybridization for prenatal and postnatal diagnosis of unbalanced chromosome abnormalities. Ann Genet. 1998;41(3):133–140. [PubMed] [Google Scholar]
  16. Lapierre J. M., Cacheux V., Luton D., Collot N., Oury J. F., Aurias A., Tachdjian G. Analysis of uncultured amniocytes by comparative genomic hybridization: a prospective prenatal study. Prenat Diagn. 2000 Feb;20(2):123–131. doi: 10.1002/(sici)1097-0223(200002)20:2<123::aid-pd762>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  17. Lestou V. S., Desilets V., Lomax B. L., Barrett I. J., Wilson R. D., Langlois S., Kalousek D. K. Comparative genomic hybridization: a new approach to screening for intrauterine complete or mosaic aneuploidy. Am J Med Genet. 2000 Jun 5;92(4):281–284. doi: 10.1002/(sici)1096-8628(20000605)92:4<281::aid-ajmg12>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  18. Levy B., Dunn T. M., Kaffe S., Kardon N., Hirschhorn K. Clinical applications of comparative genomic hybridization. Genet Med. 1998 Nov-Dec;1(1):4–12. doi: 10.1097/00125817-199811000-00004. [DOI] [PubMed] [Google Scholar]
  19. Lomax B., Tang S., Separovic E., Phillips D., Hillard E., Thomson T., Kalousek D. K. Comparative genomic hybridization in combination with flow cytometry improves results of cytogenetic analysis of spontaneous abortions. Am J Hum Genet. 2000 Mar 30;66(5):1516–1521. doi: 10.1086/302878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ludowese C. J., Thompson K. J., Sekhon G. S., Pauli R. M. Absence of predictable phenotypic expression in proximal 15q duplications. Clin Genet. 1991 Sep;40(3):194–201. doi: 10.1111/j.1399-0004.1991.tb03076.x. [DOI] [PubMed] [Google Scholar]
  21. Schultz L. N., Schmidt P., Tabor A., Bryndorf T., Christensen B., Lundsteen C. Cryptic familial t(11;18)(q25;q23) incidentally detected by interphase FISH. Clin Genet. 2001 Apr;59(4):279–283. doi: 10.1034/j.1399-0004.2001.590411.x. [DOI] [PubMed] [Google Scholar]
  22. Sutherland G. R., Eyre H. Two unusual G-band variants of the short arm of chromosome 9. Clin Genet. 1981 May;19(5):331–334. doi: 10.1111/j.1399-0004.1981.tb00719.x. [DOI] [PubMed] [Google Scholar]
  23. Warburton D. De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints. Am J Hum Genet. 1991 Nov;49(5):995–1013. [PMC free article] [PubMed] [Google Scholar]
  24. Wassman E. R., Cheyovich D. L., Nakahara Y. "Possibly" de novo translocations: prenatal risk counseling. Am J Obstet Gynecol. 1989 Sep;161(3):698–702. doi: 10.1016/0002-9378(89)90383-9. [DOI] [PubMed] [Google Scholar]

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