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DNA is hypomethylated at repetitive and single copy loci in patients with ICF syndrome

Journal Article · · American Journal of Human Genetics
OSTI ID:133753
; ;  [1]
  1. Universitaet Muenchen (Germany); and others
ICF syndrome (immunodeficiency, centromeric heterochromatin instability, facial anomaly) is a very rare genetic disorder, reported in only 12 cases. Chromosomal rearrangements occur predominantly in the heterochromatic regions of HC 1 and 16 and include stretching, whole arm deletions and multibranched configurations. The molecular defect of these abnormalities is not known. Similar abnormalities have been found in cell cultures treated with viruses or 5-acacytidine, agents which cause DNA hypomethylation. Because heterochromatic DNA is known to be highly methylated, we hypothesise that DNA hypomethylation and subsequent disturbance of heterochromatin structure may play a role in the chromosomal rearrangements of ICF syndrome. Methylation studies in DNA from peripheral lymphocytes of two non-related ICF patients revealed hypomethylation of satellite-2 DNA localized in the heterochromatic regions of HC 1 and 16. DNA hypomethylation was also found at single copy loci, e.g. D15S63, D15S9, H19 and DXS255. Differences between the two patients suggest a random distribution of DNA hypomethylation. While a causal relationship between the molecular and cytogenetic abnormalities is likely, the postulated relationship between hypomethylation and the clinical symptoms in ICF syndrome remains to be elucidated.
OSTI ID:
133753
Report Number(s):
CONF-941009--
Journal Information:
American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
Country of Publication:
United States
Language:
English