30
EIGIL KJELDSEN and STEEN K0LVRAA
(smooth brain) and a characteristic face. The syndrome is associated with
a microdeletion of chromosome 17pI3.3. Since then, FISH has proven to
be an invaluable tool for detection ofsuch submicroscopic microdeletions.
In fact, FISH has now replaced high-resolution cytogenetic approaches
when a specific microdeletion is being investigated. Thus, locus specific
probes are now available for diagnosing DiGeorge syndrome (del 22ql1.2)
(Fig. 4D shows such an example in a dual-color approach), Prader-Willi
and Angelman syndromes (del ISqll-13), retinoblastoma (del 13qI4),
Wolf-Hirschorn syndrome (del 4p13), Williams syndrome (del 7q11.23),
Rubinstein-Taybi syndrome (del 16p13.3), X-linked ichthyosis (Xp22.3),
and aniridia/Wilms tumor (delllp13) as examples and more will probably prevail. However, it should be noted that for the listed syndromes
microde1etions account for a varying degree of the etiological factors.
In for example Prader-Willi and Angelman syndromes, uniparental disomy and imprinting are also important etiological factors that cannot be
detected by FISH.
The developments of arm specific probes for each chromosome increased the possibilities for identifying and characterizing intra-chromosomal structural abnormalities that by conventional banding methods can
be difficult to ascertain (Fig. 4E).
Interphase cytogenetic diagnosis is currently used for screening prenatal samples (Kuo et al. 1991, Zahed et al. 1992) for numerical aberrations
of chromosomes 13, 18,21, X and Y (Fig. 4F). Time is often a crucial factor
and it is therefore ofgreat value that such chromosomal aberrations can be
diagnosed within one day using interphase cytogenetics in a multi-color
approach. Screening for other aneuploidies is also possible but of limited
value due to the low frequency of such abnormalities in prenatal samples.
Chromosome microdeletions have also been successfully diagnosed using
interphase cytogenetics on peripheral blood smear leukocytes (Novelli et
al. 1999). Chromosome microduplications is another group of chromosomal disorders that can be diagnosed by interphase cytogenetics (Shaffer
et al. 1997).
Mosaicism is another area where FISH-analysis is superior, as rapid
screening of a large number of metaphases or interphase nuclei can be
accomplished giving more accurate estimates of the proportion of cells
containing the chromosomal abnormality (Kalousek et aI1996). Such information is relevant for better genetic counseling as a high proportion of
cells containing an aberrant chromosome directly correlates to a more
sever phenotype (Schinzel 1983). Also, in infertility, the rapid and direct
screening of large numbers of sperm cells for aneuplodies and structural
abnormalities is important (van Hummelen et al. 1996).
EIGIL KJELDSEN and STEEN K0LVRAA
(smooth brain) and a characteristic face. The syndrome is associated with
a microdeletion of chromosome 17pI3.3. Since then, FISH has proven to
be an invaluable tool for detection ofsuch submicroscopic microdeletions.
In fact, FISH has now replaced high-resolution cytogenetic approaches
when a specific microdeletion is being investigated. Thus, locus specific
probes are now available for diagnosing DiGeorge syndrome (del 22ql1.2)
(Fig. 4D shows such an example in a dual-color approach), Prader-Willi
and Angelman syndromes (del ISqll-13), retinoblastoma (del 13qI4),
Wolf-Hirschorn syndrome (del 4p13), Williams syndrome (del 7q11.23),
Rubinstein-Taybi syndrome (del 16p13.3), X-linked ichthyosis (Xp22.3),
and aniridia/Wilms tumor (delllp13) as examples and more will probably prevail. However, it should be noted that for the listed syndromes
microde1etions account for a varying degree of the etiological factors.
In for example Prader-Willi and Angelman syndromes, uniparental disomy and imprinting are also important etiological factors that cannot be
detected by FISH.
The developments of arm specific probes for each chromosome increased the possibilities for identifying and characterizing intra-chromosomal structural abnormalities that by conventional banding methods can
be difficult to ascertain (Fig. 4E).
Interphase cytogenetic diagnosis is currently used for screening prenatal samples (Kuo et al. 1991, Zahed et al. 1992) for numerical aberrations
of chromosomes 13, 18,21, X and Y (Fig. 4F). Time is often a crucial factor
and it is therefore ofgreat value that such chromosomal aberrations can be
diagnosed within one day using interphase cytogenetics in a multi-color
approach. Screening for other aneuploidies is also possible but of limited
value due to the low frequency of such abnormalities in prenatal samples.
Chromosome microdeletions have also been successfully diagnosed using
interphase cytogenetics on peripheral blood smear leukocytes (Novelli et
al. 1999). Chromosome microduplications is another group of chromosomal disorders that can be diagnosed by interphase cytogenetics (Shaffer
et al. 1997).
Mosaicism is another area where FISH-analysis is superior, as rapid
screening of a large number of metaphases or interphase nuclei can be
accomplished giving more accurate estimates of the proportion of cells
containing the chromosomal abnormality (Kalousek et aI1996). Such information is relevant for better genetic counseling as a high proportion of
cells containing an aberrant chromosome directly correlates to a more
sever phenotype (Schinzel 1983). Also, in infertility, the rapid and direct
screening of large numbers of sperm cells for aneuplodies and structural
abnormalities is important (van Hummelen et al. 1996).