Evaluation of Patients With Unresolved Chromosome Abnormalities
Evaluation of Patients With Unresolved Chromosome Abnormalities
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
 protocol.

 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
 study.