Background: Cytogenetically visible chromosomal imbalances in humans are deleterious
and adverse in the majority of the cases. However, healthy persons living with chromosomal imbalances
in the range of several megabasepairs (Mbps) in size, like carriers of small Supernumerary
Marker Chromosomes (sSMCs) exist.
Materials & Methods: The identification of healthy sSMC carriers with euchromatic centromere-near
(ECN) imbalances led to the following proposal: ECN-regions do not contain any dosage sensitive genes.
Due to own previous work, dosage-insensitive pericentric ECN-regions were already determined with an
accuracy of 0.3 and 5 Mbp. Based on this data we established 43 new pericentromeric probe sets spanning
about 3-5 Mbp of each euchromatic human chromosome arm starting from the known insensitive
regions towards distal. Such so called pericentromeric-critical region fluorescence in situ hybridization
(PeCR-FISH) probe sets were applied exemplarily and successful here in 15 sSMC cases as available
from the Else Kröner-Fresenius-sSMC-cellbank http://ssmc-tl.com/ekf-cellbank.html.
Conclusion: Most of the involved sSMC breakpoints could be characterized as a higher resolution
than before. An unexpected result was that in 5/15 cases cryptic mosaicism was characterized. The latter
is also to be considered to have potentially an influence on the clinical outcome in these so-called
discontinuous sSMCs. Overall, the suitability of PeCR-FISH to characterize sSMCs was proven; the
potential of this probe set to further delineate sizes of dosage insensitive pericentric regions is obvious
but dependent on suited cases. Furthermore, discontinuous sSMCs can be identified by this approach
and this new subtype of sSMC needs to be studied in more detail in future.
Keywords: Molecular cytogenetics, Small Supernumerary Marker Chromosomes (sSMCs), Discontinuous sSMCs, Pericentromeric-
critical Region Fluorescence In Situ Hybridization (PeCR-FISH), Dosage insensitive genomic regions, Euchromatic
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