FISH analysis on spontaneously arising micronuclei in the ICF syndrome

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.