The purpose of this research is to study a new way to test for chromosome abnormalities.
Chromosomes are strands of DNA (the genetic material in the cell nucleus) that are made up
of genes-the units of heredity. Chromosome abnormalities are usually investigated by
staining the chromosomes with a dye (Giemsa stain) and examining them under a microscope.
This method can detect many duplications and deletions of pieces of chromosomes and is very
accurate in diagnosing certain abnormalities. It is not useful, however, for identifying
very small abnormalities. This study will evaluate the accuracy of a test method using 24
different dyes for finding small chromosome abnormalities.
Children and adults with various chromosome abnormalities may be eligible for this study,
including, for example, people with developmental delay or mental retardation, abnormal
growth features or growth retardation, and certain behavioral disorders. Participants will
be evaluated in the clinic over a 1- to 3-day period, depending on their symptoms. All
participants will be examined by a genetics specialist and will have a physical examination
and possibly X-rays, computerized tomography (CT) scans, magnetic resonance imaging (MRI),
ultrasound studies and medical photography. Blood will be drawn for chromosome
testing-about 3 tablespoons from adults and 1 to 3 teaspoons from children.
When the test results are available, participants will return to the clinic for follow-up
evaluation and review of the test findings. The genetic and medical evaluations, along with
their implications, will be discussed.
There is a range of genomic aberrations from aneuploidy down to single base pair deletions
or inserts. Present technology uses microscopic cytogenetics for detection of large
rearrangements (greater than 2 Mb) and molecular techniques for small rearrangements (less
than 2 Mb). There is a gap in practical diagnostic technology in that microscopic
cytogenetics has poor sensitivity for aberrations less than 5 Mb and the molecular
techniques are cumbersome for clinical use in the megabase range. In many cases it is
possible to determine that an aberration is present by microscopic cytogenetics but cannot
be characterized. We propose to use Spectral Karyotyping (SKY) and supplementary FISH and
molecular techniques to characterize these aberrations. Subjects will be seen in OP9 for a
clinical genetics evaluation and phlebotomy for SKY. Confirmation of SKY results will be
performed by standard FISH, genomic content mapping, and other standard techniques.
Physical anomalies or developmental anomalies.
Karyotype showing derivative chromosome abnormality that is not fully characterized.
No abnormal parental karyotype.
No prenatal specimens.
Probands of all ages, genders, and ethnic origin are eligible.
The proband must have a non-mosaic abnormal G-banded chromosome analysis of good quality
that shows one or more derivative chromosomes whose foreign component cannot be determined
by standard G-banding techniques.
The parents should also have G-banded chromosome analysis prior to eligibility for consent
2. If this has not been done by the referring physician, it may be done as part of the
The proband with the abnormal karyotype should have one or more of the following features:
dysmorphic features; developmental delay or mental retardation; growth retardation,
microephaly, short stature or failure to thrive; behavioral disorder
Biological parents must be willing to supply a blood specimen. If they have any of the
features listed above, they must attend the clinic if the proband is to be eligible.
The proband must be evaluated by the NCHGR clinical genetics service by the PI, a
co-investigator, or his associates.
Mothers will be queried about potential non-paternity. If non-paternity is possible, the
family will need to undergo clinical paternity evaluation before they are enrolled in the