title: Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays.
abstract: Chromosomal rearrangements such as microdeletions and interstitial duplications are the underlying cause of many human genetic disorders. These disorders can manifest in the form of multiple congenital anomalies (MCA), which are a significant cause of morbidity and mortality in children. The major limitations of cytogenetic tests currently used for the detection of such chromosomal rearrangements are low resolution and limited coverage of the genome. Thus, it is likely that children with MCA may have submicroscopic chromosomal rearrangements that are not detectable by current techniques. We report the use of a commercially available, oligonucleotide-based microarray for genome-wide analysis of copy number alterations. First, we validated the microarray in patients with known chromosomal rearrangements. Next, we identified previously undetected, de novo chromosomal deletions in patients with MCA who have had a normal high-resolution karyotype and subtelomeric fluorescence in situ hybridization (FISH) analysis. These findings indicate that high-density, oligonucleotide-based microarrays can be successfully used as tools for the detection of chromosomal rearrangement in clinical samples. Their higher resolution and commercial availability make this type of microarray highly desirable for application in the diagnosis of patients with multiple congenital defects.
authors.affiliation: Division of Human Genetics, Stokes Research Institute, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Ming
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Geiger
authors.forename: Alison C
authors.initials: AC
authors.lastname: James
authors.forename: Karen L
authors.initials: KL
authors.lastname: Ciprero
authors.forename: Manjunath
authors.initials: M
authors.lastname: Nimmakayalu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Andrew
authors.initials: A
authors.lastname: Huang
authors.forename: Madhavi
authors.initials: M
authors.lastname: Vaddi
authors.forename: Eric
authors.initials: E
authors.lastname: Rappaport
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.forename: Tamim H
authors.initials: TH
authors.lastname: Shaikh
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide