Human Genetics

, Volume 96, Issue 5, pp 562–571 | Cite as

DNA, FISH and complementation studies in ICF syndrome: DNA hypomethylation of repetitive and single copy loci and evidence for a trans acting factor

  • Simone Schuffenhauer
  • Oliver Bartsch
  • Markus Stumm
  • Tina Buchholz
  • Theoni Petropoulou
  • Sabine Kraft
  • Bernd Belohradsky
  • Georg Klaus Hinkel
  • Thomas Meitinger
  • Rolf-Dieter Wegner
Original Investigation

Abstract

ICF syndrome (ICFS) is a rare immunodeficiency disorder characterized by instability of the pericentromeric heterochromatin predominantly of chromosomes 1 and 16. DNA methylation studies in two unrelated ICFS patients provide further evidence for a marked hypomethylation of satellite 2 DNA. The ICFS-specific disturbances of chromatin structure take place within the satellite 2 DNA regions, as demonstrated by fluorescence in situ hybridization analysis. Moreover, methylation studies of genomic imprinted loci D15S63, D15S9, and H19 have revealed hypomethylation to different degrees in both patients; this provides evidence for hypomethylation at autosomal single copy loci in ICFS. Cell fusion experiments have revealed a distinct reduction of chromosomal abnormalities in ICFS cells after fusion with normal cells, suggesting that the abnormalities are caused by the loss of function of an as yet unknown trans acting factor. Although it is now clear that wide-spread DNA hypomethylation is a characteristic feature of ICFS, neither the cause and mechanism of hypomethylation nor their relationship to the clinical symptoms is known. We speculate that a phenotypic effect might result from tissue-dependent abnormal gene expression and/or from a possible structural disturbance of DNA domains, which, with respect to the immunodeficiency, partially prevents the normal somatic recombinations in immunologically active cells.

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Simone Schuffenhauer
    • 1
  • Oliver Bartsch
    • 2
  • Markus Stumm
    • 3
  • Tina Buchholz
    • 1
  • Theoni Petropoulou
    • 4
  • Sabine Kraft
    • 2
  • Bernd Belohradsky
    • 4
  • Georg Klaus Hinkel
    • 2
  • Thomas Meitinger
    • 1
  • Rolf-Dieter Wegner
    • 3
  1. 1.Abteilung für Pädiatrische Genetik der Kinderpoliklinik, Ludwig-Maximilians-Universität MünchenMünchenGermany
  2. 2.Institut für Klinische Genetik, Universitätsklinikum Carl Gustav Carus, Technische Universität DresdenDresdenGermany
  3. 3.Institut für Humangenetik, Freie Universität BerlinBerlinGermany
  4. 4.Dr. von Haunersches Kinderspital, Ludwig-Maximilians-Universität MünchenMünchenGermany

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