[Balanced chromosomal rearrangements resulting in intellectual disability. An analysis of 22 cases with application of CGH and FISH methods].
BACKGROUND
In approximately 6% of balanced chromosomal rearrangements carriers, intellectual disability, dysmorphic features and congenital anomalies can be found. The abnormal phenotype might be the result of genomic imbalance or aberrant expression caused by direct breakage of a dosage sensitive gene.


OBJECTIVE
To estimate the frequency and implication of the submicroscopic chromosomal aberrations on the abnormal phenotypes present in patients with balanced chromosomal rearrangements. Also an attempt was made to define the type of genetic defect and gene identification responsible for the intellectual disability and additional clinical features.


METHODS
22 patients with intellectual disability, congenital anomalies and dysmorphic features were analysed. Molecular karyotyping was performed in all patients using FISH with region-specific BAC clones, high resolution comparative genomic hybridization (HR-CGH) or array CGH (aCGH). A targeted or whole genome microarrays were applied.


RESULTS
In 5 of 22 carriers 6 microdeletions and one duplication were found (7/22, 31.8%). Only two microdeletions were mapped at the chromosomal breakpoints. Three rearrangements had more complex structure than conventional methods demonstrated. In the chromosomal breakpoints of 21 patients the 24 genes, which functions suggest the relationship between abnormal gene expression and patients' intellectual disability, were mapped.


CONCLUSIONS
We showed that in a considerable group of patients with balanced chromosomal rearrangements and abnormal phenotype the cryptic aberrations, unidentified by conventional methods, are present. These results confirmed the legitimacy of detailed analysis of the chromosomal breakpoints as well as the whole genome screening with the use of new cytogenetic methods.
Borg
Katarzyna
K
Zakład Genetyki Medycznej, Instytut Matki i Dziecka, ul. Kasprzaka 17a, 01-211 Warszawa.
Bocian
Ewa
E
Bernaciak
Joanna
J
Nowakowska
Beata
B
Derwińska
Katarzyna
K
Obersztyn
Ewa
E
Szczałuba
Krzysztof
K
Smigiel
Robert
R
Kostyk
Ewa
E
Mazurczak
Tadeusz
T
D000015:Abnormalities, Multiple / Q000235:genetics*; D002869:Chromosome Aberrations / Q000145:classification*; D002874:Chromosome Mapping / Q000379:methods; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010641:Phenotype; D014178:Translocation, Genetic