Balanced into array: genome-wide array analysis in 54 patients with an apparently balanced de novo chromosome rearrangement and a meta-analysis

Ilse Feenstra, Nicolien Hanemaaijer, Birgit Sikkema-Raddatz, Helger Yntema, Trijnie Dijkhuizen, Dorien Lugtenberg, Joke Verheij, Andrew Green, Roel Hordijk, William Reardon, Bert de Vries, Han Brunner, Ernie Bongers, Nicole de Leeuw, Conny van Ravenswaaij-Arts*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    34 Citations (Scopus)

    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. European Journal of Human Genetics (2011) 19, 1152-1160; doi:10.1038/ejhg.2011.120; published online 29 June 2011

    Original languageEnglish
    Pages (from-to)1152-1160
    Number of pages9
    JournalEuropean Journal of Human Genetics
    Volume19
    Issue number11
    DOIs
    Publication statusPublished - Nov-2011

    Keywords

    • array analysis
    • de novo translocation
    • de novo inversion
    • complex chromosome rearrangement
    • microdeletion
    • microduplication
    • MENTAL-RETARDATION
    • DEVELOPMENTAL DELAY
    • TRANSLOCATIONS
    • CGH
    • ABNORMALITIES
    • INDIVIDUALS
    • BREAKPOINTS
    • PHENOTYPES

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