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. 1995 Jul;32(7):502–508. doi: 10.1136/jmg.32.7.502

FISH analysis on spontaneously arising micronuclei in the ICF syndrome.

M Stacey 1, M S Bennett 1, M Hulten 1
PMCID: PMC1050540  PMID: 7562960

Abstract

The ICF syndrome is a rare disorder where patients show undercondensation of the heterochromatic blocks of chromosomes 1, 9, and 16 along with variable immunodeficiency. The undercondensation of the heterochromatic block appears to be restricted to a portion of PHA stimulated T cells. Patients with this syndrome also show an increase in micronuclei formation. We have used dual colour FISH to investigate the chromosomal content of these micronuclei in PHA stimulated peripheral blood cultures, an EBV transformed B cell line, and also micronuclei observed in vivo from peripheral blood smears. Chromosome 1 appears to be present in a higher proportion of micronuclei compared to chromosomes 9 and 16 in both a PHA stimulated culture and an EBV transformed cell line. An 18 centromeric probe, not associated with the ICF syndrome, showed no signal in any of the micronuclei observed. The implications from these observations are that the heterochromatic instability in the ICF syndrome is manifested not only in T but also in B cells and that it is present in vivo.

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Selected References

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  1. Becker P., Scherthan H., Zankl H. Use of a centromere-specific DNA probe (p82H) in nonisotopic in situ hybridization for classification of micronuclei. Genes Chromosomes Cancer. 1990 May;2(1):59–62. doi: 10.1002/gcc.2870020111. [DOI] [PubMed] [Google Scholar]
  2. Brinkley B. R., Tousson A., Valdivia M. M. The kinetochore of mammalian chromosomes: structure and function in normal mitosis and aneuploidy. Basic Life Sci. 1985;36:243–267. doi: 10.1007/978-1-4613-2127-9_16. [DOI] [PubMed] [Google Scholar]
  3. Carpenter N. J., Filipovich A., Blaese R. M., Carey T. L., Berkel A. I. Variable immunodeficiency with abnormal condensation of the heterochromatin of chromosomes 1, 9, and 16. J Pediatr. 1988 May;112(5):757–760. doi: 10.1016/s0022-3476(88)80698-x. [DOI] [PubMed] [Google Scholar]
  4. Cooke H. J., Hindley J. Cloning of human satellite III DNA: different components are on different chromosomes. Nucleic Acids Res. 1979 Jul 25;6(10):3177–3197. doi: 10.1093/nar/6.10.3177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eden S., Cedar H. Role of DNA methylation in the regulation of transcription. Curr Opin Genet Dev. 1994 Apr;4(2):255–259. doi: 10.1016/s0959-437x(05)80052-8. [DOI] [PubMed] [Google Scholar]
  6. Ellard S., Parry E. M. Induction of micronuclei in V79 Chinese hamster cells by hydroquinone and econazole nitrate. Mutat Res. 1993 May;287(1):87–91. doi: 10.1016/0027-5107(93)90147-8. [DOI] [PubMed] [Google Scholar]
  7. Fasth A., Forestier E., Holmberg E., Holmgren G., Nordenson I., Söderström T., Wahlström J. Fragility of the centromeric region of chromosome 1 associated with combined immunodeficiency in siblings. A recessively inherited entity? Acta Paediatr Scand. 1990 Jun-Jul;79(6-7):605–612. doi: 10.1111/j.1651-2227.1990.tb11524.x. [DOI] [PubMed] [Google Scholar]
  8. Fryns J. P., Azou M., Jaeken J., Eggermont E., Pedersen J. C., Van den Berghe H. Centromeric instability of chromosomes 1, 9, and 16 associated with combined immunodeficiency. Hum Genet. 1981;57(1):108–110. doi: 10.1007/BF00271181. [DOI] [PubMed] [Google Scholar]
  9. Gimelli G., Varone P., Pezzolo A., Lerone M., Pistoia V. ICF syndrome with variable expression in sibs. J Med Genet. 1993 May;30(5):429–432. doi: 10.1136/jmg.30.5.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Guttenbach M., Schmid M. Exclusion of specific human chromosomes into micronuclei by 5-azacytidine treatment of lymphocyte cultures. Exp Cell Res. 1994 Mar;211(1):127–132. doi: 10.1006/excr.1994.1068. [DOI] [PubMed] [Google Scholar]
  11. Hennig U. G., Rudd N. L., Hoar D. I. Kinetochore immunofluorescence in micronuclei: a rapid method for the in situ detection of aneuploidy and chromosome breakage in human fibroblasts. Mutat Res. 1988 Dec;203(6):405–414. doi: 10.1016/0165-1161(88)90013-1. [DOI] [PubMed] [Google Scholar]
  12. Howard P. J., Lewis I. J., Harris F., Walker S. Centromeric instability of chromosomes 1 and 16 with variable immune deficiency: a new syndrome. Clin Genet. 1985 May;27(5):501–505. doi: 10.1111/j.1399-0004.1985.tb00239.x. [DOI] [PubMed] [Google Scholar]
  13. Jeanpierre M., Turleau C., Aurias A., Prieur M., Ledeist F., Fischer A., Viegas-Pequignot E. An embryonic-like methylation pattern of classical satellite DNA is observed in ICF syndrome. Hum Mol Genet. 1993 Jun;2(6):731–735. doi: 10.1093/hmg/2.6.731. [DOI] [PubMed] [Google Scholar]
  14. Kieback P., Wendisch H., Lorenz P., Hinkel K. ICF-Syndrom. Immundefizienz, chromosomale Zentromerinstabilität, faziale Anomalien. Fallvorstellung und Literaturübersicht. Monatsschr Kinderheilkd. 1992 Feb;140(2):91–94. [PubMed] [Google Scholar]
  15. Knuutila S., Nylund S. J., Wessman M., Larramendy M. L. Analysis of genotype and phenotype on the same interphase or mitotic cell. A manual of MAC (morphology antibody chromosomes) methodology. Cancer Genet Cytogenet. 1994 Jan;72(1):1–15. doi: 10.1016/0165-4608(94)90102-3. [DOI] [PubMed] [Google Scholar]
  16. Larramendy M. L., Knuutila S. Increased frequency of micronuclei in B and T8 lymphocytes from smokers. Mutat Res. 1991 Feb;259(2):189–195. doi: 10.1016/0165-1218(91)90052-n. [DOI] [PubMed] [Google Scholar]
  17. Majone F., Semmes O. J., Jeang K. T. Induction of micronuclei by HTLV-I Tax: a cellular assay for function. Virology. 1993 Mar;193(1):456–459. doi: 10.1006/viro.1993.1145. [DOI] [PubMed] [Google Scholar]
  18. Maraschio P., Cortinovis M., Dainotti E., Tupler R., Tiepolo L. Interphase cytogenetics of the ICF syndrome. Ann Hum Genet. 1992 Jul;56(Pt 3):273–278. doi: 10.1111/j.1469-1809.1992.tb01152.x. [DOI] [PubMed] [Google Scholar]
  19. Maraschio P., Tupler R., Dainotti E., Piantanida M., Cazzola G., Tiepolo L. Differential expression of the ICF (immunodeficiency, centromeric heterochromatin, facial anomalies) mutation in lymphocytes and fibroblasts. J Med Genet. 1989 Jul;26(7):452–456. doi: 10.1136/jmg.26.7.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Maraschio P., Zuffardi O., Dalla Fior T., Tiepolo L. Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome. J Med Genet. 1988 Mar;25(3):173–180. doi: 10.1136/jmg.25.3.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Miller B. M., Nüsse M. Analysis of micronuclei induced by 2-chlorobenzylidene malonitrile (CS) using fluorescence in situ hybridization with telomeric and centromeric DNA probes, and flow cytometry. Mutagenesis. 1993 Jan;8(1):35–41. doi: 10.1093/mutage/8.1.35. [DOI] [PubMed] [Google Scholar]
  22. Miniou P., Jeanpierre M., Blanquet V., Sibella V., Bonneau D., Herbelin C., Fischer A., Niveleau A., Viegas-Péquignot E. Abnormal methylation pattern in constitutive and facultative (X inactive chromosome) heterochromatin of ICF patients. Hum Mol Genet. 1994 Dec;3(12):2093–2102. doi: 10.1093/hmg/3.12.2093. [DOI] [PubMed] [Google Scholar]
  23. Moyzis R. K., Albright K. L., Bartholdi M. F., Cram L. S., Deaven L. L., Hildebrand C. E., Joste N. E., Longmire J. L., Meyne J., Schwarzacher-Robinson T. Human chromosome-specific repetitive DNA sequences: novel markers for genetic analysis. Chromosoma. 1987;95(6):375–386. doi: 10.1007/BF00333988. [DOI] [PubMed] [Google Scholar]
  24. Ren L., Zhang H., Yang J., Zhang Z. A sequential study on the use of the cytokinesis-block micronucleus method in mouse splenocytes. Mutat Res. 1993 Apr;301(4):223–227. doi: 10.1016/0165-7992(93)90061-y. [DOI] [PubMed] [Google Scholar]
  25. Rocchi M., Archidiacono N., Ward D. C., Baldini A. A human chromosome 9-specific alphoid DNA repeat spatially resolvable from satellite 3 DNA by fluorescent in situ hybridization. Genomics. 1991 Mar;9(3):517–523. doi: 10.1016/0888-7543(91)90419-f. [DOI] [PubMed] [Google Scholar]
  26. Rosin M. P., German J. Evidence for chromosome instability in vivo in Bloom syndrome: increased numbers of micronuclei in exfoliated cells. Hum Genet. 1985;71(3):187–191. doi: 10.1007/BF00284570. [DOI] [PubMed] [Google Scholar]
  27. Schmid M., Haaf T., Grunert D. 5-Azacytidine-induced undercondensations in human chromosomes. Hum Genet. 1984;67(3):257–263. doi: 10.1007/BF00291352. [DOI] [PubMed] [Google Scholar]
  28. Smeets D. F., Moog U., Weemaes C. M., Vaes-Peeters G., Merkx G. F., Niehof J. P., Hamers G. ICF syndrome: a new case and review of the literature. Hum Genet. 1994 Sep;94(3):240–246. doi: 10.1007/BF00208277. [DOI] [PubMed] [Google Scholar]
  29. Sternes K. L., Vig B. K. Micronuclei, kinetochores and hypoploidy: tests with some agents. Mutagenesis. 1989 Nov;4(6):425–431. doi: 10.1093/mutage/4.6.425. [DOI] [PubMed] [Google Scholar]
  30. Tiepolo L., Maraschio P., Gimelli G., Cuoco C., Gargani G. F., Romano C. Multibranched chromosomes 1, 9, and 16 in a patient with combined IgA and IgE deficiency. Hum Genet. 1979 Oct 1;51(2):127–137. doi: 10.1007/BF00287166. [DOI] [PubMed] [Google Scholar]
  31. Titenko-Holland N., Moore L. E., Smith M. T. Measurement and characterization of micronuclei in exfoliated human cells by fluorescence in situ hybridization with a centromeric probe. Mutat Res. 1994 Feb;312(1):39–50. doi: 10.1016/0165-1161(94)90007-8. [DOI] [PubMed] [Google Scholar]
  32. Turleau C., Cabanis M. O., Girault D., Ledeist F., Mettey R., Puissant H., Prieur M., de Grouchy J. Multibranched chromosomes in the ICF syndrome: immunodeficiency, centromeric instability, and facial anomalies. Am J Med Genet. 1989 Mar;32(3):420–424. doi: 10.1002/ajmg.1320320331. [DOI] [PubMed] [Google Scholar]
  33. Valkova G., Ghenev E., Tzancheva M. Centromeric instability of chromosomes 1, 9 and 16 with variable immune deficiency. Support of a new syndrome. Clin Genet. 1987 Mar;31(3):119–124. doi: 10.1111/j.1399-0004.1987.tb02781.x. [DOI] [PubMed] [Google Scholar]
  34. Yager J. W., Eastmond D. A., Robertson M. L., Paradisin W. M., Smith M. T. Characterization of micronuclei induced in human lymphocytes by benzene metabolites. Cancer Res. 1990 Jan 15;50(2):393–399. [PubMed] [Google Scholar]

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