The Principles of Clinical Cytogenetics - Extra Materials - Springer

464 Daynna Wolff and Stuart Schwartz
Table 3
Marker Chromosome Assessment
Associated syndrome/phenotypea Type of marker FISH probe result (estimated risk for abnormality)*
ESAC Pancentromeric, no α-satellite High risk for abnormality; phenotype
dependent on euchromatin present
Bisatellited/
monocentric
α-sat +: 13/21, 14/22, 15 General risk for bi-sat = 11%
idic(15) SNRPN–positive ~0% risk
SNRPN–negative 95%–MR
idic(22) ATP6E–present 5%–MR (usually resulting from UPD)
Cat-eye syndrome
Monosatellited α-sat +: 13/21, 14/22 No general risk, dependent on whether
euchromatic material present
Nonsatellited α-Satellite present General risk for nonsatellited = 11%
metacentric α-Satellite present for 8, 9,
12, or 18 centromere
If metacentric, risk for MR = ~100%
Sex chromosome DXZ1 (X centromere) +
XIST–positive Turner syndrome only > 95%
XIST–negative
DYZ3 (Y centromere)
Majority–MR
SRY–positive Male phenotype
SRY–negative Female phenotype
a Data from refs. 28 and 29.
determining the chromosomal origin of such markers. However, this information does not usually
allow for specific clinical risk estimations for genetic counseling (see Chapter 20). In a research
setting, once the origin of the marker has been determined, single-copy probes in both the p and q
pericentromeric regions can be studied to assist in karyotype/phenotype correlations.
Prenatal Studies
Fluorescence in situ hybridization has been widely used for the detection and analysis of prenatal
chromosomal abnormalities (see Chapter 12). One major advantage of FISH technology is the ability to
study uncultured material to produce a rapid result. In addition, FISH is useful for characterizing or detecting
subtle abnormalities not delineated by routine banding (e.g., deletions, markers, or duplications).
PLOIDY ANALYSIS
The vast majority of abnormalities detected prenatally are aneuploidies, involving chromosomes
13, 18, 21, or the sex chromosomes. FISH provides rapid ploidy assessment of these chromosomes
by utilizing probes on uncultured interphase cells. In most cases, five probes are used and applied to
two different slides (or two different sections of a single slide). α-Satellite DNA for the X chromosome
and chromosome 18 is used together with a classical satellite probe for the Y chromosome,
using three different probe colors. The other mix consists of single-copy probes for both chromosomes
13 and 21, using two different colors. These studies will ascertain numerical abnormalities for
these chromosomes (see Fig. 7) and will also detect triploidy.
In 1992, Klinger et al. (42) first demonstrated the feasibility of detecting aneuploidy in uncultured
amniocytes by using FISH in a prospective study. They constructed probes derived from specific
subregions of chromosomes 13, 18, 21, X, and Y and analyzed 526 samples in a blind fashion. All 21
abnormal samples were correctly identified in this study. Since this initial work, a number of studies
have validated this approach (see Table 4.)