Abstract
Congenital heart disease (CHD) is the most common type of birth defect, and the etiology of most cases is unknown. CHD often occurs in association with other birth malformations, and only in a minority are disease-causing chromosomal abnormalities identified. We hypothesized that children with CHD and additional birth malformations have cryptic chromosomal abnormalities that might be uncovered using recently developed DNA microarray-based methodologies. We recruited 20 children with diverse forms of CHD and additional birth defects who had no chromosomal abnormality identified by conventional cytogenetic testing. Using whole-genome array comparative genomic hybridization, we screened this population, along with a matched control population with isolated heart defects, for chromosomal copy number variations. We discovered disease-causing cryptic chromosomal abnormalities in five children with CHD and additional birth defects versus none with isolated CHD. The chromosomal abnormalities included three unbalanced translocations, one interstitial duplication, and one interstitial deletion. The genetic abnormalities were predominantly identified in children with CHD and a neurologic abnormality. Our results suggest that a significant percentage of children with CHD and neurologic abnormalities harbor subtle chromosomal abnormalities. We propose that children who meet these two criteria should receive more extensive genetic testing to detect potential cryptic chromosomal abnormalities.
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Abbreviations
- CGH:
-
comparative genome hybridization
- CHD:
-
congenital heart disease
- CNV:
-
copy number variation
- RT qPCR:
-
real-time quantitative polymerase chain reaction
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Acknowledgements
We thank the participating subjects and families; C. Rains for research coordinator support; T. Hyatt in the McDermott Center for Human Growth and Development, and G. Bartov in the UT Southwestern Cytogenetics Laboratory for technical assistance. Divisions of Cardiology and Cardiothoracic Surgery at Children's Medical Center Dallas for assistance with clinical information; and Drs. W. A. Scott and M. Maitra for critical review of the manuscript.
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Richards, A., Santos, L., Nichols, H. et al. Cryptic Chromosomal Abnormalities Identified in Children With Congenital Heart Disease. Pediatr Res 64, 358–363 (2008). https://doi.org/10.1203/PDR.0b013e31818095d0
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DOI: https://doi.org/10.1203/PDR.0b013e31818095d0
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