Cryptic chromosomal abnormalities identified in children with congenital heart disease.
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.
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Ashleigh A
AA
Richards
Lane Jaeckle
LJ
Santos
Haley A
HA
Nichols
Bill P
BP
Crider
Frederick F
FF
Elder
Natalie S
NS
Hauser
Andrew R
AR
Zinn
Vidu
V
Garg
D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D046228:Microarray Analysis