The Principles of Clinical Cytogenetics - Extra Materials - Springer

462 Daynna Wolff and Stuart Schwartz
Table 2
Subtelomeric Studies
Study (ref.) No. studied Ascertainment Frequency
Knight et al. (1999) (18) 284 Moderate to severe retardation 7.4%
182 Mild retardation 0.5%
Rossi et al. (2001) (21) 200 Idiopathic mental retardation 6.5%
Joyce et al. (2002) (16) 200 Unexplained developmental delay 0%
Clarkson et al. (2002) (23) 50 Idiopathic mental retardation 4%
Riesel et al. (2001) (19) 252 Mild to severe mental retardation 5.2%
Anderlid et al. (2002) (23) 50 Idiopathic mental retardation 9%
Jalal et al. (2003) (20) 372 Idiopathic mental retardation 6.8%
Baker et al. (2002) (24) 53 Idiopathic mental retardation (isolated) 1.9%
197 Idiopathic MR (dysmorphic features) 4.1%
Popp et al. (2002) (17) 30 Unexplained developmental retardation 13.3%
Duplications and Marker Chromosomes
Characterization of de novo duplication and marker chromosomes has valuable implications with
respect to phenotype/karyotype correlation. FISH is the optimal method for such studies.
Approximately 70% of chromosomal duplications are intrachromosomal, whereas 30% involve a
nonhomologous chromosome (27). Thus, for the majority of cases, FISH with a single chromosomal
library or locus-specific probe from the chromosome with the abnormality will confirm the origin of the
duplicated material. There are two basic ways to approach the identification of extra nonhomologous
(interchromosomal) material: initial recognition by G-banding and subsequent confirmation with a
chromosomal library or locus-specific probe, or multicolor FISH (M-FISH) (see the section Specialized
and Evolving FISH Technologies, below).
With quality high-resolution chromosome studies, the suspected origin of the majority of interchromosomal
duplications might be limited to a few chromosomal regions. Thus, duplications
usually are confirmed with FISH for one to four chromosomal libraries (see Fig. 5). If there is no
“best guess” based on the banding studies, M-FISH (see below) can be performed to identify the
material’s chromosomal origin. In many cases, once the chromosomal origin is determined by M-
FISH, the cytogeneticist can then re-examine the G-banding pattern and determine the bands involved.
However, additional probes might be needed to resolve the exact duplication. Alternatively,
pan-subtelomeric probes may be used to ascertain the chromosomal arm from which the material
originated.
Chromosomes that are unidentifiable by routine banding are termed “markers” (see Chapters 3
and 8). Marker chromosomes represent a heterogeneous group and are typically extra structurally
abnormal chromosomes (ESACs). The most common types of marker, for which clinical phenotypes
have been defined, can be fully characterized using FISH (see Table 3). Other types of markers can
be partially defined by FISH, and the impact of these chromosomes on the clinical phenotype often
cannot be reliably predicted.
In general, there are two basic methods for delineating the chromosomal origin of marker chromosomes.
These include identification by using M-FISH or utilizing individual chromosomal libraries
or α-satellite DNA probes. M-FISH can identify the chromosomal origin of many markers. However,
this methodology will not always allow for an understating of the implication of the markers, as the
exact chromosomal region of origin cannot be determined with these methods. An alternative approach
is to initially use a pancentromeric probe to determine if α-satellite DNA is present in the marker and
then to use chromosome-specific α-satellite probes to establish the origin. Although analphoid markers
are rare, if there is not α-satellite DNA present as determined by the lack of signal using the