Detection of deletions in de novo "balanced" chromosome rearrangements: further evidence for their role in phenotypic abnormalities.
OBJECTIVE
The purpose of this study was to test the hypothesis that deletions of varying sizes in de novo apparently balanced chromosome rearrangements are a significant cause of phenotypic abnormalities.


METHODS
A total of fifteen patients, with seemingly balanced de novo rearrangements by routine cytogenetic analysis but with phenotypic anomalies, were systematically analyzed. We characterized the breakpoints in these fifteen cases (two of which were ascertained prenatally), using a combination of high-resolution GTG-banding, fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes (BACs), and data from the Human Genome Project.


RESULTS
Molecular cytogenetic characterization of the 15 patients revealed nine with deletions, ranging in size from 0.8 to 15.3 Mb, with the number of genes lost ranging from 15 to 70. In five of the other six cases, a known or putative gene(s) was potentially disrupted as a result of the chromosomal rearrangement. In the remaining case, no deletions were detected, and no known genes were apparently disrupted.


CONCLUSIONS
Our study suggests that the use of molecular cytogenetic techniques is a highly effective way of systematically delineating chromosomal breakpoints, and that the presence of deletions of varying size is an important cause of phenotypic abnormalities in patients with "balanced" de novo rearrangements.
Astbury
Caroline
C
Center for Human Genetics and Department of Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106-9959, USA.
Christ
Laurie A
LA
Aughton
David J
DJ
Cassidy
Suzanne B
SB
Kumar
Arun
A
Eichler
Evan E
EE
Schwartz
Stuart
S
D002871:Chromosome Banding; D022202:Chromosomes, Artificial, Bacterial; D041321:Chromosomes, Human, X / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D017353:Gene Deletion; D015321:Gene Rearrangement / Q000235:genetics* / Q000502:physiology; D016045:Human Genome Project; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010641:Phenotype; D013056:Spectrophotometry, Ultraviolet