Abnormal methylation pattern in constitutive and facultative heterochromatin of ICF patients

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133726

Miniou, P; Blanquet, V; Viegas-Pequignot, E ^[1]

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1. Hopital Necker-Enfants Malades, Paris (France); and others

ICF syndrome is a rare autosomal recessive disease, characterized by variable immunodeficiency, centromeric instability and facial abnormalities. Stretchings and frequent associations of centromeric or juxtacentromeric heterochromatin of chromosome 1 and 16 principally, and to a lesser degree, chromosome 9 mimic chromosome features of normal PHA-stimulated lymphocytes treated with 5-azacytidine, an inducer of demethylation. In fact, in these patients we have detected by DNA digestion with methyl-sensitive enzymes a hypomethylation of classical satellites 2 and 3, located in heterochromatin. To assess the role of other satellite DNA in the heterochromatin modifications and chromosome rearrangements, in situ fluorescent method using 5-methylcytosine (5-MeC) monoclonal antibody on chromosomes and nuclei were performed in parallel with Southern blot analysis of other satellite sequences located in heterochromatin. 5-MeC reveals that constitutive and facultative heterochromatin (X inactive chromosome) are hypomethylated. Alpha satellite sequences corresponding to centromeric heterochromatin of chromosomes 1, 3, 6, 9, 16, 18 and X are mostly methylated in patients G and R, and are undermethylated in patient S. Both molecular and cytogenetic analysis are in agreement. By in situ hybridization, breakpoints of rearranged chromosomes were located in stretched and hypomethylated classical satellites. In euchromatin, 5-MeC antibodies reveal an R-like banding pattern indicating an unequal distribution of DNA methylation, disclosing another aspect of chromosome organization. The underlying hypomethylation, associated with an abnormal chromatin structure, may predispose to chromosome instability.

• OSTI ID: 133726
• 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

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BANDING TECHNIQUES
CENTROMERES
CONGENITAL MALFORMATIONS
DNA
DNA HYBRIDIZATION
DNA SEQUENCING
FLUORESCENCE
HEREDITARY DISEASES
HETEROCHROMATIN
HUMAN CHROMOSOMES
INSTABILITY
METHYLATION
PATIENTS
RECESSIVE MUTATIONS