The Principles of Clinical Cytogenetics - Extra Materials - Springer

Fluorescence In Situ Hybridization 465
Fig. 6. A dicentric chromosome hybridized with dual-color chromosome 15 probes, including both an
α-satellite DNA probe (green) along with a single-copy SNRPN probe (red). Signals from both probes are
present on the normal chromosomes 15. The marker chromosome (arrow) has two α-satellite DNA signals,
confirming that it is dicentric. In addition, the marker contains two copies of the SNRPN probe. A control probe
for the distal long arm was also included; signals are only present on the normal chromosomes 15, not on the
marker chromosome. This abnormality was ascertained in a 6-year-old female with hypotonia, behavior difficulties,
learning problems, and autism.
A number of technological advances led to improvement of the initial prenatal FISH studies. These
include a direct labeled probe set consisting of three repetitive DNA probes (18, X, and Y) and two
single-copy DNA probes localized to the long arms of chromosome 13 and 21, and significantly
improved methods for preparing uncultured cells for analysis.
Although this technology can provide answers within 24 hours of obtaining a sample, it is limited
in that it can only detect aneuploidies for a limited number of chromosomes (13, 18, 21, X, and Y). In
a 5-year collaborative study, a total of 146,128 amniocenteses were performed revealing a total of
4163 abnormalities; however, only 69.4% of these would have been detected using interphase analysis
of uncultured amniotic fluid cells (41). A similar number (65–70%) has been proposed in a position
statement by the American College of Medical Genetics (ACMG)/American Society of Human
Genetics (ASHG). The statement indicates that the detection rate would increase to 80% with increasing
age because of the association of increased age and nondisjunction.
Overall, prenatal FISH technology has been found to be effective, sensitive, and specific.
Tepperberg et al. (38) reported on a 2-year multicenter retrospective analysis and review of literature
of the AneuVysion assay (Vysis, Inc.). Of the 29,039 studies they were able to document, there was