title: Balanced into array: genome-wide array analysis in 54 patients with an apparently balanced de novo chromosome rearrangement and a meta-analysis.
abstract: High-resolution genome-wide array analysis enables detailed screening for cryptic and submicroscopic imbalances of microscopically balanced de novo rearrangements in patients with developmental delay and/or congenital abnormalities. In this report, we added the results of genome-wide array analysis in 54 patients to data on 117 patients from seven other studies. A chromosome imbalance was detected in 37% of all patients with two-breakpoint rearrangements. In 49% of these patients, the imbalances were located in one or both breakpoint regions. Imbalances were more frequently (90%) found in complex rearrangements, with the majority (81%) having deletions in the breakpoint regions. The size of our own cohort enabled us to relate the presence of an imbalance to the clinical features of the patients by using a scoring system, the De Vries criteria, that indicates the complexity of the phenotype. The median De Vries score was significantly higher (P=0.002) in those patients with an imbalance (5, range 1-9) than in patients with a normal array result (3, range 0-7). This study provides accurate percentages of cryptic imbalances that can be detected by genome-wide array analysis in simple and complex de novo microscopically balanced chromosome rearrangements and confirms that these imbalances are more likely to occur in patients with a complex phenotype.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Ilse
authors.initials: I
authors.lastname: Feenstra
authors.forename: Nicolien
authors.initials: N
authors.lastname: Hanemaaijer
authors.forename: Birgit
authors.initials: B
authors.lastname: Sikkema-Raddatz
authors.forename: Helger
authors.initials: H
authors.lastname: Yntema
authors.forename: Trijnie
authors.initials: T
authors.lastname: Dijkhuizen
authors.forename: Dorien
authors.initials: D
authors.lastname: Lugtenberg
authors.forename: Joke
authors.initials: J
authors.lastname: Verheij
authors.forename: Andrew
authors.initials: A
authors.lastname: Green
authors.forename: Roel
authors.initials: R
authors.lastname: Hordijk
authors.forename: William
authors.initials: W
authors.lastname: Reardon
authors.forename: Bert de
authors.initials: Bd
authors.lastname: Vries
authors.forename: Han
authors.initials: H
authors.lastname: Brunner
authors.forename: Ernie
authors.initials: E
authors.lastname: Bongers
authors.forename: Nicole de
authors.initials: Nd
authors.lastname: Leeuw
authors.forename: Conny
authors.initials: C
authors.lastname: van Ravenswaaij-Arts
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D002869:Chromosome Aberrations; D056905:Chromosome Breakpoints; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D015894:Genome, Human; D006801:Humans; D059785:Karyotype; D008297:Male; D010641:Phenotype