The Principles of Clinical Cytogenetics - Extra Materials - Springer

200 Kathleen Kaiser-Rogers and Kathleen Rao
short arms, the stalk region sandwiched between encodes ribosomal RNA. Typically, many copies of
these ribosomal RNA genes are located within the stalk region of each of the five pairs of acrocentric
chromosomes. This region of the genome is therefore highly redundant, and the presence of missing
or extra copies of this sequence is of no phenotypic consequence. Translocation of this region to
another chromosome, provided that critical genes have not been deleted or interrupted secondary to
the rearrangement, also appears to have no clinical consequences. Multiple examples of de novo and
familial normal variant chromosomes with terminal translocations and interstitial insertions of these
ribosomal RNA sequences have been documented in the literature.
In addition to the common C-band heterochromatic and acrocentric short arm variants described
earlier, numerous other variant chromosomes also exist in the human karyotype. Some of these actually
appear to involve duplications and deletions of apparent euchromatic (expressed) DNA. Because
no phenotype is associated with an altered copy number of these sequences, it is assumed that the
genes within them are not dosage sensitive. As one might suspect, these variants appear to be rarer
than those described earlier and they can cause a great deal of consternation when they are observed
in a karyotype.
Unless a variant chromosome is very common, most cytogeneticists would agree that the variation
should be reported and follow-up familial studies should be offered in an attempt to document the
same variation in at least one other normal family member. If the variant chromosome is a rare one,
particularly if it is one that appears to represent duplication or deletion of euchromatic material, an
attempt might be made to (1) document the variant chromosome in multiple normal family members
and (2) further characterize the variant chromosome using molecular techniques such as FISH (see
Chapter 17). This more extensive work-up would be done to ensure that one has correctly interpreted
the rearrangement and has not overlooked the presence of imprinting or a more complex rearrangement
with reproductive consequences for the family.
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