Molecular refinement of karyotype: beyond the cytogenetic band.
OBJECTIVE
Illustrate the use of molecular methodologies to delineate subtle, de novo, chromosome aberrations and determine the presence, or absence, of known genes, allowing improved predictions of long-term phenotypic effect.


METHODS
High-resolution chromosome analysis followed by FISH and microsatellite analysis to determine the extent and parental origin of the abnormalities.


RESULTS
Four de novo deletions involving chromosomes 5q, 10q, and 16p were delineated molecularly. Specific genes were shown to be, or not to be, involved in each aberration, refining karyotype-genotype correlation.


CONCLUSIONS
Molecular characterization of subtle chromosomal aberrations can provide information to assist in predicting clinical outcome in cases involving genes known to have an effect due to haploinsufficiency or aberrant gene dosage.
Department of Genetics and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Ohio 44106-9959, USA.
D A
DA
Sirko-Osadsa
S B
SB
Cassidy
T W
TW
Depinet
N H
NH
Robin
C
C
Limwongse
S
S
Schwartz
D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D018244:Chromosomes, Artificial, Yeast; D002879:Chromosomes, Human, Pair 10; D002885:Chromosomes, Human, Pair 16; D002895:Chromosomes, Human, Pair 5; D003582:Cytogenetics / Q000379:methods*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping / Q000379:methods*; D008297:Male; D018895:Microsatellite Repeats; D008957:Models, Genetic; D010641:Phenotype